Promethease Report

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. 23an...

rs1800460 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the rs1142345(G) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatm...

A form of this snp, located upstream of the XPNPEP2 gene on the X chromosome, may cause susceptibility to skin swelling when taking medicines called ACE Inhibitors. Also known as -2399C/A in the literature; however in SNPedia, where the orientation of the corresponding dbSNP entry is recognized as primary, this is G/T. After noticing the association of this SNP with the phenotype, the authors genotyped 20 independent AE-ACEi cases and 60 unrelated, matching controls for this SNP. The T allele was present in 8 of the 20 AE patients; and by allele counting, the T allele was found at a frequency of 11.1% in the control population and 27.3% in their AE-ACEi cases. *See also OMIM 300145 [OMIM:?]

After taking Acetaminophen (Tylenol®), rs1467558(A;G) individuals have higher alanine aminotransferase (ALT) levels, a sign of liver toxicity, than do (G;G) homozygotes. More studies are needed; there was only 1 (A;A) individual, and he didn't show elevated ALT levels; furthermore, the ALT increases were 'modest' anyway for (A;G) individuals compared to (G;G). see also: 23andMe blog '''Note:''' the orientation of this SNP in SNPedia is as detailed in dbSNP, but in publications (including 23andMe's blog) the orientation is 'flipped', so what's (A;A) in dbSNP is (T;T) as discussed by the 23andMe blog.

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs3774426 is a SNP in the calcium channel, voltage-dependent, L type, alpha 1D subunit CACNA1D gene. A study of 161 Japanese patients (85 men, 76 women) being treated for hypertension with L-type dCCBs (calcium channel blockers) concluded that individuals with rs3774426(C;C) genotypes responded better, as measured by lowered systolic and diastolic blood pressure readings.

rs5065, also known as T2238C, is a SNP in the atrial natriuretic precursor A NPPA gene. A large study has been conducted in which 42,418 hypertensive participants 55 or older were followed for several years while on one of four medications: a diuretic, a calcium antagonist, an angiotensin-converting enzyme inhibitor, or an alpha-blocker. The primary endpoint was either fatal heart disease or a heart attack. The blood pressure after six months of rs5065(G;G) patients (note: genotype is in dbSNP orientation, not as published) was lower if the patients were treated with diuretics compared to other medications, with smaller variation seen for (A;A) genotypes. The authors noted that none of the findings retained statistical significance after correction for multiple comparisons, but since the t...

rs312481 is a SNP in the calcium channel, voltage-dependent, L type, alpha 1D subunit CACNA1D gene. A study of 161 Japanese patients (85 men, 76 women) being treated for hypertension with L-type dCCBs (calcium channel blockers) concluded that individuals with rs312481(C;C) genotypes responded better, as measured by lowered systolic and diastolic blood pressure readings.

No literature was known for this SNP, rs527974, as of Jan 2012. It was added to SNPedia based on a misreading of an abstract. For future reference, position 527974 in GenBank NT_009759.15, which is the position referred to in , is NC_000012.11:g.2602925 in HGVS nomenclature, and as mentioned above, this position does not have an rsid in dbSNP.

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

Trajectories of change in depression severity during treatment with antidepressants. Pharmacogenomics of antidepressant drugs.

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs4794067(C;C) and rs4794067(C;T) genotypes for the TBX21 gene are calculated to be at 2.15 fold higher risk (CI: 1.26-3.64) for aspirin-induced asthma (AIA) compared to rs4794067(T;T) homozygotes, based on a study of 72 patients vs 640 controls in a study of a Japanese population. Note that in this population, but perhaps not others, linkage disequilibrium exists between this SNP located upstream of the gene, rs4794067, and a common synonymous SNP located in the first exon, rs2074190, with a predictive accuracy of 92%. On the other hand, rs4794067(C;C) may greatly decrease the risk of lupus if rs17250932(C;C) is also present (at least in Chinese people). And those 2 SNPs also reduce the risk of intractable Graves' disease (at least in Japanese people).

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. 23an...

rs1800460 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the rs1142345(G) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatm...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

part of a three marker haplotype rs737865-rs4680-rs165599 COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. We have typed the IVS 1 rs737865 and 3' rs615599 sites and also included a novel IVS 1 indel polymorphism. We report that the schizophrenia-associated haplotype is significantly heterogeneous in populations worldwide. may affect non-Hodgkin lymphoma, anxiety-related personality traits Also mentioned in these PMIDs * * * * * * [PharmGKB:Curated This variant may predict a favorable outcome for bupropion treatment for smoking cessation] [OMIM:CATECHOL-O-METHYLTRANSFERASE; COMT]

rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. For historic reasons, the rs762551(C) allele is considered the wild-type, even though it is the rarer allele in most populations. The rs762551(A) allele is the 'fast metabolizer' allele known as CYP1A2*1F; the (C) allele is by comparison a slower metabolizer of certain substrates (including caffeine). In terms of genotypes, only rs762551(A;A) individuals are considered fast metabolizers. Individuals who are rs762551(A;C) heterozygotes or rs762551(C;C) homozygotes are both considered slow metabolizers. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. One well known substrate of CYP1A2 is caffeine; individuals who are ca...

rs4410790 and rs2470893 influence habitual caffeine consumption Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk. Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. [GWAS:None]

rs4410790 and rs2470893 influences habitual caffeine consumption [GWAS:None]

Variation at this SNP, rs5751876, also referred to as 1976C>T or 1976T>C, appears to influence how an individual responds to moderate levels (150mg) of caffeine. T/T carriers displaying significantly increased subjective levels of anxiety after consumption. However a PharmGKB variant annotation suggests it is (C;C) genotypes who are more sensitive to caffeine. rs5751876 is not associated with how much coffee one drinks, though, nor with risk for Parkinson's disease, based on a study of 1,200 subjects. 'rs2298383 shows functional potential based on in silico analyses and might therefore represent the true underlying causal variant'

rs34983651 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs5839491

Helps to identify HLA-B*1502 [PharmGKB:Curated Risk or phenotype-associated allele: allele 4. Phenotype: Combined alleles of rs3909184 (2) and rs2844682 (4) are tagging SNPs for HLA-B*1502 (0.011 allele frequency). Study size: 45. Study population/ethnicity: Unrelated Han Chinese from Beijing, China. Significance metric(s): Type of association: GN]

rs1051740, also known as Tyr113His, is a SNP in the microsomal epoxide hydrolase EPHX1 gene. severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection with the allele HLA-A*3101 and rs1051740(C;C) [PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy, the maternal EPHX1 113 H (rs1051740 T/C) allele was associated with craniofacial abnormalities in the child. Study size: 157 pregnancies. Study population/ethnicity: phenytoin use during the first trimester and maternal epilepsy. metric(s): per rare allele OR: 2.43, 95% confidence interval (CI): 1.16-5.10, P=0.02. Type of asso...

rs2273697, also known as c1249G>A or p.V471I, is a nonsynonymous polymorphism in the ABCC2 gene. From an initial case-control study of 146 patients with epilepsy, followed by replication (p=0.001) in another 279 patients, the rs2273697(A) allele was associated with neurological adverse drug reactions from taking carbamazepine. Functional studies showed that this SNP selectively reduced carbamazepine transport across the cell membrane. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This SNP showed a strong association with the neurological adverse drug reaction caused (ADR) by carbamazepine (P=0.005). The study results indicate that the c.1249A variant is an independent risk factor of carbamazepine CNS ADR. Study size: 146 patients with epilepsy who had been prescr...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs5065, also known as T2238C, is a SNP in the atrial natriuretic precursor A NPPA gene. A large study has been conducted in which 42,418 hypertensive participants 55 or older were followed for several years while on one of four medications: a diuretic, a calcium antagonist, an angiotensin-converting enzyme inhibitor, or an alpha-blocker. The primary endpoint was either fatal heart disease or a heart attack. The blood pressure after six months of rs5065(G;G) patients (note: genotype is in dbSNP orientation, not as published) was lower if the patients were treated with diuretics compared to other medications, with smaller variation seen for (A;A) genotypes. The authors noted that none of the findings retained statistical significance after correction for multiple comparisons, but since the t...

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. 23an...

23andMe blog hearing loss linked to a chemotherapy drug named Cisplatin. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with cisplatin-induced hearing loss from a large candidate gene screen in 2 pediatric cohorts.. Study size: 54 (discovery); 112 (replication). Study population/ethnicity: Children with neoplasms receiving cisplatin; Canada. Significance metric(s): OR = 5.52 (CI 1.91, 15.95); p = 0.000182 Type of association: CO; TOX; ADR] [OMIM:?]

rs4675690 is in close proximity to CREB1, and adjacent to LOC151194. g2b2mh blog individuals with the TT genotype at rs4675690 (C/T) showed less disgust, but not happiness, desire or fear. T allele associated with increased chance of suicide (OR = 2.3, 95% CI 1.3-2.9, TT homozygotes vs CC homozygotes?) during the first 30 days (p > 0.05 after the first month) of citalopram treatment, in a study of 1447 citalopram users (male only subgroup, 539 in total). Two haplotypes (see below) also showed significant association with suicidality in the male subgroup. *rs2709376(C),rs2253206(A),rs7569963(A),rs7594560(T),rs4675690(C) - common haplotype, reduced chance of suicide in males, p = 0.004 *rs2709376(C),rs2253206(A),rs7569963(G),rs7594560(T),rs4675690(T) - increased chance of suicide in males...

Pharmacogenetics of antidepressant response. [GWAS:Treatment response to citalopram]

[GWAS:Treatment response to citalopram]

[GWAS:Treatment response to citalopram]

[GWAS:Treatment response to citalopram]

[GWAS:Treatment response to citalopram]

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

This SNP, located in an intron of the GRIA3 gene (also known as AMPA3), has been linked in one study to increased thoughts of suicide in patients taking the anti-depressant drug citalopram. The increased risk is calculated to be 1.9x. If the individual is also carrying two rs2518224(C) alleles, i.e. is a rs2518224(C;C) homozygote, the odds ratio for having suicidal thoughts is increased to ~15x (CI: 3.7 - 60.6). [PharmGKB:Curated This SNP in the GRIA3 gene was associated with treatment-emergent suicidal ideation during citalopram therapy in a clinically representative cohort of outpatients with major depressive disorder. DNA samples from 1,915 participants were genotyped.]

This SNP, located in an intron of the GRIK2 gene, has been linked in one study to increased thoughts of suicide in patients using the anti-depressant drug citalopram. The risk is only seen for individuals carrying two rs2518224(C) alleles, i.e. the rs2518224(C;C) homozygotes. The odds ratio for these individuals is 8.2. If the individual also has at least one rs4825476(G) allele, the odds ratio for having suicidal thoughts is increased to ~15x (CI: 3.7 - 60.6). [PharmGKB:Curated This SNP in the GRIK2 gene was associated with treatment-emergent suicidal ideation during citalopram therapy in a clinically representative cohort of outpatients with major depressive disorder. DNA samples from 1,915 participants were genotyped.]

rs7569963 is directly adjacent to CREB1. Associated with significantly (p = 0.005) increased chance of suicide in a study of 1447 citalopram users (male only subgroup, 539 in total). Two haplotypes (see below) also showed significant association with suicidality in the male subgroup. *rs2709376(C),rs2253206(A),rs7569963(A),rs7594560(T),rs4675690(C) - common haplotype, reduced chance of suicide in males, p = 0.004 *rs2709376(C),rs2253206(A),rs7569963(G),rs7594560(T),rs4675690(T) - increased chance of suicide in males, p = 0.009 [PharmGKB:Curated In a nested case-control study derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study this SNP in the CREB1 gene was associated with treatment-emergent suicidality among men with depression.]

rs1954787, located in an intron of the GRIK4 gene, was found to be associated with a somewhat increased rate of successful response to treatment of depression with the drug citalopram. From the abstract of this article: 'The effect size of (this) GRIK4 marker alone was modest, but homozygote carriers of the treatment-response-associated marker alleles of both the GRIK4 and HTR2A (see rs7997012) genes were 23% less likely to experience nonresponse to (citalopram) treatment relative to participants who did not carry any of these marker alleles.' * See also Anxiety Blog posting [PharmGKB:Curated A study in 1,816 eligible patients from the STAR*D cohort found that genetic variation in a kainic acid-type glutamate receptor is reproducibly associated with response to the antidepressant citalopr...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 3 x 10^-7 for triglycerides as a result of clozapine use

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 4 x 10^-7 for total cholesterol as a result of clozapine use

rs1057868, also known as A503V, is a relatively common variant defining the POR*28 allele of the P450 (cytochrome) oxidoreductase POR gene. The POR gene encodes a protein involved in electron transport of cytochrome p450 enzymes such as CYP3A4, CYP3A5 and CYP3A7. A study of 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity found that CYP3A SNPs themselves did not predict particularly well inter-individual variability in overall CYP3A activity. However, rs1057868(T;T) individuals had a 1.6x increased CYP3A activity compared to rs1057868(C) carriers (n=182, p=0.004), and the finding was replicated in a second independent dataset. The authors conclude that this POR gene SNP is a better predictor of overall CYP3...

rs1414334(C) associated with the metabolic syndrome in patients using *clozapine (OR, 9.20; 95% CI, 1.95-43.45) *risperidone (OR, 5.35; 95% CI, 1.26-22.83) [PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: In a replication study, the C allele of HTR2C rs1414334 polymorphism is associated with development of the metabolic syndrome during treatment with antipsychotics. Study size: 186. Study population/ethnicity: 93% Caucasian; European; Dutch; The Netherlands. Significance metric(s): OR = 3.73; 95% CI= 1.29-10.79; P = 0.015. Type of association: CO.]

In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene . In humans, SNPs in the equivalent RGS2 gene have now been studied to see if they are correlated to anxiety related disorders. In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other RGS2 SNPs, carriers of a rs4606(G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026). In the second part of this study, 744 college undergraduates (228 men, 516 women) w...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

The rs4880(T) allele, part of the codon for amino acid valine at codon 16 of the antioxidant protein from the mitochrondrial superoxide dismutase 2 SOD2 gene, is the most common in most populations studied. The rs4880(C) allele gives rise to an alanine at this position is it also known as Val16Ala manganese superoxide dismutase, or A16V. There appears to be some conflict in the literature over the effect of this SNP. Having a valine at codon 16 is said to reduce enzyme activity , and thus lead to increased oxidative stress, yet in at least one study of the actual enzyme levels measured in people, SOD2 activity was 33% higher in (C;T) or (T;T) individuals compared to (C;C) individuals . Regardless of how this resolves, several phenotypic associations have been reported for this SNP, includi...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

This SNP, in the GSTP1 gene influences asthma risk; the (A) allele encodes the Ile, while the (G) allele encodes the Val. This SNP is also known as GSTP1Val105, or GSTP1 Ile105Val. Despite evidence of antioxidant effects of vitamin E in vitro and in animal studies, large, randomized clinical trials have not substantiated a benefit of vitamin E in reducing inflammation in humans. In healthy control subjects, the effect of α-tocopherol supplementation on the production of inflammatory cytokines appears to be dependent on an individual's genotype. These genotype-specific differences may help explain some of the discordant results in studies that used vitamin E. Persons having the alleles AA or AG had an increase in interleukin-6 (IL-6) upon supplementing alpha-tocopherol (the most common form...

rs12762549 and rs11045585 can be used to predict whether docetaxel will induce leukopenia/neutropenia, according to a study of ~100 Japanese patients. When patients were classified into three groups by the scoring system based on the genotypes of these two SNPs, patients with a score of 1 or 2 were shown to have a significantly higher risk of docetaxel-induced leukopenia/neutropenia as compared to those with a score of 0 (P = 0.0000057; odds ratio [OR], 7.00; 95% CI [confidence interval], 2.95-16.59). This prediction system correctly classified 69.2% of severe leukopenia/neutropenia and 75.7% of non-leukopenia/neutropenia into the respective categories. [Effect percentages provided in table are raw population fractions taken from the referenced study based on rs11045585 only. Total populat...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

escitalopram response [GWAS:Response to antidepressants]

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs25532 is a SNP in a regulatory region upstream of the serotonin transporter SLC6A4 gene. The more common allele, rs25532(C), is the higher-expressing allele. A study of patients with obsessive compulsive disorder (OCD) concluded that the major allele of rs25532 was a major contributor to the association of a corresponding haplotype with this disorder. [PharmGKB:Curated This study found that the minor allele of the functional C > T single nucleotide polymorphism, rs25532, located less than 150 nucleotides centromeric of the serotonin transporter-linked polymorphic region indel (known as 5-HTTLPR) significantly decreased luciferase reporter gene expression levels by 15-80%, depending on 5-HTTLPR allele background and cell type.]

This SNP in the GABRA2 gene has been linked to Alcoholism. The effect of this SNP, a synonymous change at amino acid residue 132, is unknown, but it does not change the GABRA2 protein sequence. Carriers of at least one rs279858(G) allele respond slower to the effects of alcohol and are thereby apparently more prone to alcoholism than carriers of two rs279858(A) alleles. Finasteride, an FDA approved drug for the treatment of benign prostatic hypertrophy and a modulator of GABRA2, was shown to have more of a blocking effect on rs279858(A) homozygotes. Note that nearby SNPs have been grouped into a haplotype that shows statistically stronger association with alcohol dependence, namely the haplotype consisting of the rs279871(A) + rs279845(T) + rs279836(A) alleles . 1050 nicotine-dependent cas...

In HLA-B*5701 carrier cases, i.e. rs2395029(G) carriers, rs10937275 showed an increased in risk for drug-induced liver injury for patients taking flucloxacillin. The odds ratio was 4.1 (p = 1.4 x 10(-8)). [PharmGKB:Curated This intronic variant of ST6GAL1 was significantly associated with flucloxacillin-induced liver injury in a GWAS screen (OR = 4.1, P = 1.4x10-8).] [OMIM:HLA COMPLEX P5 GENE; HCP5]

rs242941 is a SNP in the corticotrophin-releasing hormone receptor 1 CRHR1 gene. (G;G) better response to inhaled corticosteroids fluticasone propionate and salmeterol in patients with COPD in a Korean study with 84 subjects. [PharmGKB:Curated Haplotype tagging SNP.]

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs34983651 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs5839491

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

journal When using lithium as a treatment for Bipolar disorder rs9784453 appears to be associated with time to recurrence of a mood episode while on. By my reading of Figure 3, the median time to recurrence is about 230 days for homozygote carriers with the 'poor response' allele and about 520 days for homozygote carriers with the 'good response' allele, with heterozygote carriers falling in between.

Although not associated with increased risk for developing bipolar disorder, amongst those with it, the (G) allele of this SNP has been reported to have a somewhat protective effect in that individuals who have a (G) allele develop bipolar disorder at a later age than those with the more common (A;A) genotypes. Also known as the -50T/C SNP from this GSK3-beta (GSK3B) gene. may effect lithium treatment response - C allele carriers showed considerably greater response with lithium treatment, with remissions of 56.25% after 4 weeks compared to 31% for T/T carriers [PharmGKB:Curated This variant is in the promoter region of GSK3B. T allele is associated with greater transcription activity compared with the A allele. This variant is associated with antidepressant treatment response in Chinese ...

rs734312, or '''His611Arg''', is a SNP located in exon 8 of the WFS1 gene. An A at this SNP encodes for histamine and a G encodes for arginine. A single study found this SNP to be associated with medication overuse headache (sample consisting of 82 MOH patients). Compared to the His/His genotypes, those carrying two Arg alleles had a significantly higher monthly drug consumption (p = 0.00075) and higher severe depressive scores on the Beck Depression Index (p = 0.003). His611Arg is also potentially implicated in type-2 diabetes. In a sample of 3,234 high diabetes risk individuals, Arg/Arg carriers had a generally higher insulinogenic index and lower insulin sensitivity levels, while His allele carriers followed the opposite pattern. Arg/Arg carriers also responded strongly to metformin and...

rs1128503 is a SNP in the transporter P-glycoprotein (P-gp) 170, encoded by the ABCB1 (also known as MDR1) gene. Methadone is a substrate of this protein, so variants may affect the efficacy and optimal dosage of this drug as used for treating opiate dependence. A study of 98 methadone-maintaining patients concluded that the higher (>150 mg/day) and lower (< or =150 mg/day) methadone dose groups differed significantly in their rs1128503 status (experiment-wise p = 0.0325). Furthermore, individuals with the 3-locus genotype pattern (T;T)-(T;T)-(T;T) for SNPs rs1045642, rs2032582 and rs1128503, respectively, had an approximately 5-fold chance of requiring the 'higher' methadone dose, while individuals heterozygous for these three SNPs have an approximately 3-fold chance of stabilizing ...

rs1057868, also known as A503V, is a relatively common variant defining the POR*28 allele of the P450 (cytochrome) oxidoreductase POR gene. The POR gene encodes a protein involved in electron transport of cytochrome p450 enzymes such as CYP3A4, CYP3A5 and CYP3A7. A study of 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity found that CYP3A SNPs themselves did not predict particularly well inter-individual variability in overall CYP3A activity. However, rs1057868(T;T) individuals had a 1.6x increased CYP3A activity compared to rs1057868(C) carriers (n=182, p=0.004), and the finding was replicated in a second independent dataset. The authors conclude that this POR gene SNP is a better predictor of overall CYP3...

This SNP, located in the 3' UTR of the CSNK1E gene, has been associated with sensitivity to the acute effects of d-amphetamine. Sensitivity to psychoactive drugs has been associated with potential to develop drug abuse. The more sensitive allele is rs135745(C). However, in a separate study, this SNP did not affect susceptibility to methamphetamine dependence or psychosis, at least in a Japanese population. Note: orientation relative to dbSNP needs to be confirmed/checked.

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs4680 (Val158Met) is a well studied SNP in the COMT gene. 23andMe blog summarizes them as *rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions *rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis; summary at ) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compar...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

This SNP is associated with a higher risk of liver injury in patients taking the nonsteroidal anti-inflammatory drug lumiracoxib, which has been withdrawn from most markets.

People with one or two copies of the G allele at this SNP are 3.5 times more likely to suffer liver injury than TT carriers when taking the prescription nonsteroidal anti-inflammatory drug (NSAID) lumiracoxib. This new pain medication was approved in Europe in late 2006, but because of a higher incidence of liver injury and patient deaths than among patients using other NSAIDs, it was withdrawn from the market in most countries. It is still sold in some countries under the brand names Prexige and Joicela.

nortriptyline response [GWAS:Response to antidepressants]

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs6280, also known as '''Ser9Gly''', is a SNP in the dopamine receptor D3 DRD3 gene. The rs6280(C) allele encodes a glycine, and the (T) allele encodes a serine (in dbSNP orientation). In a study of 88 patients being treated for schizophrenia with olanzapine, those who were rs6280(C;C) homozygotes had greater positive symptom remission (endpoint rating of minimal or none on all PANSS clinical response positive items, 39.1%), as compared with (C;T) or (T;T) genotypes (13.8%; p = 0.033). Ser9Gly has been implicated in executive function in some studies, but the results are conflicting. * Gly/Gly carriers showed significantly (p = 0.002) poorer performance than Ser/Ser carriers on executive functioning tasks in a somewhat small Caucasian sample (84 patients with first-episode psychosis and 85...

rs4765623 is a SNP in the scavenger receptor class B, member 1 SCARB1 gene. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs4765623(C) allele were more likely to gain significant weight compared to rs4765623(T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs5092 and rs7412, were also significantly associated with weight profiles in these patients. Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA. [GWAS:None]

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 4 x 10^-7 for total cholesterol as a result of olanzapine use

rs3813929, also known as -759C/T, is a SNP in the 5-hydroxytryptamine (serotonin) receptor 2C HTR2C gene. A study of 107 patients with schizophrenia being treated with olanzapine reported a protective effect against weight-gain from the (T) allele of this SNP; zero patients (of 28) with a rs3813929(T) allele had a body mass index increase of >=10% (p=0.002), whereas (C;C) homozygotes did. This effect may also involve nearby SNP rs518147. T allele showed borderline significant association with higher BMI and incidence of lifetime major depressive disorder among 4978 persons from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, however, only the association with BMI remained borderline significant within the full EPIC-Norfolk cohort (20,981 persons) The association...

In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene . In humans, SNPs in the equivalent RGS2 gene have now been studied to see if they are correlated to anxiety related disorders. In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other RGS2 SNPs, carriers of a rs4606(G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026). In the second part of this study, 744 college undergraduates (228 men, 516 women) w...

rs5092 is a SNP in the apolipoprotein A4 APOA4 gene. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs5092(G) allele were less likely to gain significant weight compared to rs5092(A;A) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs4765623 and rs7412, were also significantly associated with weight profiles in these patients.

rs518147, also known as -697G/C, is a SNP in the 5-hydroxytryptamine (serotonin) receptor 2C HTR2C gene. A study of 107 patients with schizophrenia being treated with olanzapine reported a protective effect against weight-gain from the (C) allele of this SNP; fewer patients (of 28) with a rs518147(C) allele had a body mass index increase of >=10% (p=0.0006), whereas (G;G) homozygotes did. This effect may also involve nearby SNP rs3813929. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depression. HTR2C gene ...

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

rs4680 (Val158Met) is a well studied SNP in the COMT gene. 23andMe blog summarizes them as *rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions *rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis; summary at ) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compar...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs6314, also known as C1354T or His452Tyr/H452Y, is a SNP in the serotonin 2A receptor HTR2A gene. Based on a study of 166 Caucasian patients being treated for depression with paroxetine, rs6314 heterozygotes were associated with better response. There was a significantly higher frequency of heterozygotes in the remitter and response groups in comparison to the non-remitter (odds ratio 7.50, p=0.002) and non-response groups (odds ratio 5.25, p=0.01). * rs6314 is part of a 4-SNP haplotype in the serotonin 2A receptor gene HTR2A that has been associated with rheumatoid arthritis in a study of 1800 European patients. The risk allele is rs6314(C). The overall risk for the haplotype CTCC of SNPs rs6311-rs1328674-rs6313-rs6314 is 1.68 (CI: 1.20 - 2.34, p = 0.02). Note: the orientation of rs13286...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs11740584 is one of two SNPs in the IL4 gene that is (somewhat) associated with penicillin allergy, based on a relatively small study of 23 cases and 39 controls, t the other SNP being rs10062446.

rs10062446 is one of two SNPs in the IL4 gene that is (somewhat) associated with penicillin allergy, based on a relatively small study of 23 cases and 39 controls, t the other SNP being rs11740584.

In one large Swedish study, men with one or two rs2987983(C) alleles were reported to be at somewhat increased (odds ratio 1.22) risk for Prostate cancer compared to men homozygous for the wild type rs2987983(T) allele, however the risk can be reduced by adding phytoestrogens to the diet. [PharmGKB:Curated Haplotype tagging SNP.] [OMIM:ESTROGEN RECEPTOR 2; ESR2]

rs4680 (Val158Met) is a well studied SNP in the COMT gene. 23andMe blog summarizes them as *rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions *rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis; summary at ) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compar...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

rs8179183 is a SNP in the leptin receptor LEPR gene. In a study of 101 mostly Caucasian patients prescribed the atypical antipsychotic risperidone, carriers of a rs8179183(G) allele were less likely to gain significant weight compared to rs8179183(C;C) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs6837793 and rs705381, were also significantly associated with weight profiles in these patients. [OMIM:LEPTIN RECEPTOR POLYMORPHISM]

rs6837793 is a SNP associated with the NPY5 receptor gene, located in the single promoter region likely to be co-regulating the Y1 and Y5 receptor genes. In a study of 101 mostly Caucasian patients prescribed the atypical antipsychotic risperidone, carriers of a rs6837793(G) allele were more likely to gain significant weight compared to rs6837793(A;A) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs8179183 and rs705381, were also significantly associated with weight profiles in these patients.

rs8179183 is a SNP in the leptin receptor LEPR gene. In a study of 101 mostly Caucasian patients prescribed the atypical antipsychotic risperidone, carriers of a rs8179183(G) allele were less likely to gain significant weight compared to rs8179183(C;C) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs6837793 and rs705381, were also significantly associated with weight profiles in these patients. [OMIM:LEPTIN RECEPTOR POLYMORPHISM]

rs167771 was significantly associated with autism spectrum disorder in a study of 144 patients. G allele associated with increased extra-pyramidal symptom risk as a result of risperidone treatment in a study of 321 psychiatric inpatients (81 presenting with EPS and 189 without) [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: The G variant of rs167771 was associated with increased risk for extrapyramidal symptoms in psychiatric patients receiving risperidone. Study size: 132. Study population/ethnicity: Patients with Schizophrenia or Bipolar disorder receiving antipsychotics; Caucasians; Spain; Catalonia. Significance metric(s): OR = 3.3; p = 0.00013. Type of association: PD.]

rs1176713 is a SNP, also known as g.14396A>G, in the 5-hydroxytryptamine (serotonin) receptor 3A HTR3A gene. rs1176713 may be a useful predictor of therapeutic response to risperidone treatment in Chinese schizophrenia patients

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 3 x 10^-7 for hip circumference as a result of risperidone use

rs6837793 is a SNP associated with the NPY5 receptor gene, located in the single promoter region likely to be co-regulating the Y1 and Y5 receptor genes. In a study of 101 mostly Caucasian patients prescribed the atypical antipsychotic risperidone, carriers of a rs6837793(G) allele were more likely to gain significant weight compared to rs6837793(A;A) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs8179183 and rs705381, were also significantly associated with weight profiles in these patients.

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 1 x 10^-8 for hip circumference as a result of risperidone use

rs1414334(C) associated with the metabolic syndrome in patients using *clozapine (OR, 9.20; 95% CI, 1.95-43.45) *risperidone (OR, 5.35; 95% CI, 1.26-22.83) [PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: In a replication study, the C allele of HTR2C rs1414334 polymorphism is associated with development of the metabolic syndrome during treatment with antipsychotics. Study size: 186. Study population/ethnicity: 93% Caucasian; European; Dutch; The Netherlands. Significance metric(s): OR = 3.73; 95% CI= 1.29-10.79; P = 0.015. Type of association: CO.]

rs3813928 (-995G>A / G-995A) is a SNP upstream of HTR2C. in a small sample of 45 autistic patients taking risperidone for up to one year, HTR2A Rs6311 (-1438G>A), DRD3 rs6280 (Ser9Gly), HTR2C rs3813928 (995G>A) and ABCB1 rs1128503) (1236C>T) were predictive of risperidone response Identification of functional SNPs in the 5-prime flanking sequences of human genes. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. [PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: Carriers of the A variant of HTR2C:(-995)G>A had higher Autism Treatment Evaluation Checklist (ATEC) scores, indica...

In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene . In humans, SNPs in the equivalent RGS2 gene have now been studied to see if they are correlated to anxiety related disorders. In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other RGS2 SNPs, carriers of a rs4606(G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026). In the second part of this study, 744 college undergraduates (228 men, 516 women) w...

G allele associated with schizophrenia among 120 (likely Japanese) first-episode neuroleptic-naive schizophrenics treated with risperidone genotyped for 30 variants in misc. dopamine and serotonin (receptors and otherwise) two SNPs in DRD2 (rs1799989 and rs1800497) and two SNPs in AKT1 (rs3803300 and rs2494732) were significant predictors of treatment response to risperidone The ancestral allele is G in the dbSNP database. [PharmGKB:Curated This SNP is significant predictor of treatment response to risperidone in first-episode schizophrenia.]

rs1801028 is a SNP in the dopamine D2 receptor DRD2 gene. A meta-analysis comprising 27 samples and over 3,707 schizophrenia patients concluded that Cys/Ser heterozygotes, i.e. rs1801028(C;G) genotypes, were at elevated risk for schizophrenia when compared to either homozygote genotype (rs1801028(C;C) or rs1801028(G;G)). The odds ratio was 1.4 (p<0.005). An earlier meta-analysis comprising over 9,000 schizophrenia patients concluded pretty much the same thing: the Cys311 (rs1801028(G)) allele frequency led to an odds ratio of 1.43 (CI: 1.16-1.78, p<0.001) for this risk allele. A study of ~120 Chinese patients with schizophrenia concluded that Cys/Ser heterozygotes may not respond to risperidone treatment as well as Ser/Ser homozygotes. A paper has been published describing mistakes m...

A total of 262 Korean type-2 diabetes patients were treated with 12 weeks of rosiglitazone at 4mg/day and genotyped to reveal that rs10192566(G) allele carriers responded better than (C) carriers. Patients with rs10192566(G) alleles had a larger decrease in fasting plasma glucose, 2-h postprandial glucose, and HbA1c than rs10192566(C;C) homozygotes. None of the other LPIN1 gene SNPs tested were associated with response. Note: rs11693809, rs10192566, and rs2278513 are in nearly complete linkage disequilibrium (D'>0.958, r(2) >0.882). [PharmGKB:Curated A study in patients with type 2 diabetes treated with rosiglitazone showed that this SNP in the LPIN1 gene was significantly associated with rosiglitazone treatment response. rs11693809 and rs2278513 are in nearly complete linkage diseq...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

[GWAS:Response to statin therapy]

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

[GWAS:Response to statin therapy]

rs4693596(C;C) 2x odds of myopathy when taking statins. Statin Response

[GWAS:Response to statin therapy]

[GWAS:Response to statin therapy]

rs2306283 (Asn130Asp/N130D, A388G/388A>G) is a SNP within SLCO1B1 (Solute carrier organic anion transporter family member 1B1). A G at this location denotes the SLCO1B1*1B allele. among 8 healthy volunteers with *1B/*1B genotypes and 16 with the *1A/*1A genotype, *1B/*1B genotype associated with reduced plasma concentrations of repaglinide (but not nateglinide) consistent with increased hepatic uptake by SLCO1B1 (but w/ limited effects on nateglinide pharmacokinetics) news rs2306283 influences statin-related myopathy risk Genotyping panel for assessing response to cancer chemotherapy. Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism...

[GWAS:Response to statin therapy]

[GWAS:Response to statin therapy]

influences statin response *rs72559745 (SLCO1B1*1) AA AA *rs56061388 (SLCO1B1*3) TT TT *rs4149056 (SLCO1B1*5) TT TT *rs55901008 (SLCO1B1*6) TT TT

[GWAS:Response to statin therapy]

influences statin response *rs72559745 (SLCO1B1*1) AA AA *rs56061388 (SLCO1B1*3) TT TT *rs4149056 (SLCO1B1*5) TT TT *rs55901008 (SLCO1B1*6) TT TT

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

rs3740065 is a SNP in the ATP-binding cassette, sub-family C (CFTR/MRP), member 2 ABCC2 gene. A study of 282 hormone receptor-positive, invasive breast cancer Japanese patients receiving tamoxifen found a significant association with shorter recurrence-free survival (p = .00017; hazard ratio 10.64, CI: 1.44 - 78.88) in rs3740065(T;T) patients; the hazard ratio for carriers of one (T) allele was 3.5 (CI: 0.5-26). Curiously, no significant difference in plasma levels of the tamoxifen metabolites endoxifen or 4-hydroxytamoxifen were seen. This same study of tamoxifen users concluded that rs3740065(T;T) patients who also had two CYP2D6 risk alleles had a 45 fold higher risk of recurrence than patients with zero or one (out of the possible four) risk alleles. The overall average recurrence risk...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs12762549 and rs11045585 can be used to predict whether docetaxel will induce leukopenia/neutropenia, according to a study of ~100 Japanese patients. When patients were classified into three groups by the scoring system based on the genotypes of these two SNPs, patients with a score of 1 or 2 were shown to have a significantly higher risk of docetaxel-induced leukopenia/neutropenia as compared to those with a score of 0 (P = 0.0000057; odds ratio [OR], 7.00; 95% CI [confidence interval], 2.95-16.59). This prediction system correctly classified 69.2% of severe leukopenia/neutropenia and 75.7% of non-leukopenia/neutropenia into the respective categories. [Effect percentages provided in table are raw population fractions taken from the referenced study based on rs11045585 only. Total populat...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

After taking Acetaminophen (Tylenol®), rs1467558(A;G) individuals have higher alanine aminotransferase (ALT) levels, a sign of liver toxicity, than do (G;G) homozygotes. More studies are needed; there was only 1 (A;A) individual, and he didn't show elevated ALT levels; furthermore, the ALT increases were 'modest' anyway for (A;G) individuals compared to (G;G). see also: 23andMe blog '''Note:''' the orientation of this SNP in SNPedia is as detailed in dbSNP, but in publications (including 23andMe's blog) the orientation is 'flipped', so what's (A;A) in dbSNP is (T;T) as discussed by the 23andMe blog.

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

Several SNPs in the VKORC1 gene have been linked to warfarin sensitivity, with perhaps the most common being this SNP rs9923231. Note that the orientation as published in scientific articles is often on the opposite strand compared to the orientation in dbSNP, so you will sometimes see it as a G>T snp. It is also known as *-1639G>A with the minus indicating that this is in an upstream promoter *3673 based on its position in GenBank accession number AY587020. *VKORC1*2. The main findings related to the treatment of venous thromboembolism (aka VTE; from hypercoagulability) with the blood thinner warfarin for this SNP are that carriers of the rs9923231(T) allele require significantly reduced doses of warfarin, and are (otherwise) at a higher risk of serious bleeding. Clinical studies de...

rs2108622 is a SNP in the cytochrome P450, family 4, subfamily F, polypeptide 2 CYP4F2 gene. In the males rs2108622(G) was significantly higher in cerebral infarction patients (P = 0.025) A study of Italian patients concluded that rs2108622(T;T) patients require 5.49 mg/day of warfarin versus 2.93 mg/day for (C;C) patients. Analysis of variance indicates that about 7% of mean weekly warfarin dose variance is explained by CYP4F2 genotype. A study of 370 Brazilian ('admixed') patients concludes that prospective CYP4F2 genotyping is of little value to these patients, presumably due to ethnic-based differences. [PharmGKB:Curated Risk or phenotype-associated allele: no allelic association. Phenotype: Improved pharmacogenetic algorithm-based warfarin dosing. Study size: 370. Study population/et...

rs8050894, is located on chromosome 16 in the gene VKORC1. VKORC1 is the primary target of the drug warfarin (Coumadin), a commonly used oral anticoagulant. rs8050894 is one of several polymorphisms found in VKORC1 that is associated with specific warfarin doses (). Other polymorphisms in VKORC1 (rs7196161, rs9923231, rs9934438, rs2359612) are equally predictive of warfarin dose requirement in both European and Asian-descent individuals. Other polymorphisms found in the gene cytochrome P450 2C9 (CYP2C9) influence the metabolism of warfarin and have a smaller effect on warfarin dose. These polymorphisms are rs1799853 (CYP2C9*2) and rs1057910 (CYP2C9*3). In several hundred Europeans, no association was found between rs8050894 and risk for ischemic stroke. Genetic-based dosing in orthopedic p...

[PharmGKB:Curated In a GWAS study, this SNP accounted for ~25% of the variance in log-transformed stabilized warfarin dose, and was in perfect linkage disequilibrium with rs9923231 (VKORC1:-1639).] [GWAS:Warfarin maintenance dose]

influences warfarin dose [PharmGKB:Non-Curated This intronic variant in the membrane calcium-channel gene CACNA1C was correlated with warfarin dose (p = 9.2 × 10−5) in the index population (n = 181) from a GWAS study of white patients undergoing anticoagulation therapy. Combined analysis of the index and replication populations (n = 374) yielded a p value of 8.6 × 10−7. "However, this variant did not reach established significance threshold independently in the replication population (P = .002), nor did it achieve significance after multiple testing correction in multivariate modeling (uncorrected P = .003)".] [GWAS:Warfarin maintenance dose]

rs11676382 was associated with a warfarin maintenance dose across all analysis methods. the effects of GGCX are potentially population/treatment-dependent and will not have broad utility for determining warfarin dosing.

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...