Promethease Report

spitoon rs2180439(T;T) have 2x increased odds of male pattern baldness. [omim:ALOPECIA, ANDROGENETIC, 3; AGA3] [GWAS:Male-pattern baldness]

This SNP influences skin pigmentation. The allele p.A111T, rs1426654(A), indicates light-skinned european ancestry. It appears as if this SNP is a relatively new one in human evolution; one estimate is that the rs1426654(A) allele, in other words, light skin pigmentation, spread through the European population around 6,000 - 12,000 years ago. Prior to that, 'European ancestors' were most likely relatively brown-skinned. This SNP is one of three from the SLC24A5 gene that can be analyzed to categorize the ancestry of a person as either European, African, or Asian, based on a 2009 study. The 3 SNPs are: * rs1426654 * rs2555364 * rs16960620 [omim:SOLUTE CARRIER FAMILY 24 (SODIUM/POTASSIUM/CALCIUM EXCHANGER), MEMBER]

This SNP also goes under the name M170. As such, it has been recognized as one of the most reliable indicators of Y haplogroup I. The mutation from A to C indicates membership of the European haplogroup I (nearly one out of five Europeans is a member). Haplogroup I probably arose in Europe because it is almost non-existent outside of Europe. [haplogroup:?]

This SNP, along with SNPs rs6910071 and rs3817964, is a tag SNP for the HLA-DRB1*0401 allele. The HLA-DRB1*0401 allele has been associated with higher risk for rheumatoid arthritis, and in particular, rheumatoid vasculitis. The association is seen particularly for individuals carrying two copies of, i.e. homozygous for, the allele. The reported odds ratio for rs660895(G;G) homozygotes is 6.2 (CI: 1.01 - 37.9). The risk for rheumatoid arthritis may be higher for individuals carrying one copy (one 'dose') of the HLA-DRB1*0401 allele, if they also carry a different HLA-DRB1 risk allele. In particular, *0401/*0404 individuals are reported to have an odds ratio for rheumatoid vasculitis of 4.1 (CI: 1.1 - 16.2), and *0401/*0101 individuals have an odds ratio of 4.0 (CI: 1.4 - 11.6). *(A;A) is 0 ...

rs6983267 is a SNP on chromosome 8q24, associated with increased risk for several cancers, particularly prostate cancer. In studies dividing the 8q24 region, this SNP falls in region 3. In a study of over 3,600 Caucasians with prostate cancer, rs6983267 is one of five SNPs used (with family history as a sixth factor) to cumulatively predict overall risk. On their own, the rs6983267(G;G) and (G;T) risk genotypes yield an odds ratio for developing prostate cancer of 1.37 (CI: 1.18-1.59, p=3.4-10e-5) and may account for 22.2% of population attributable risk. The increased risk of developing prostate cancer associated with rs6983267 now appears to be independent of the risk associated with it's close neighbor, rs1447295. The odds ratio for heterozygotes is estimated to be 1.26 (CI: 1.13 - 1.41...

rs4146894, a SNP in the PLEKHA1 gene, is associated with increased risk for age related macular degeneration based on a study of 118 Caucasians. The odds ratio for risk of AMD was 9.1 (CI: 4.0-20.9, p=0.0001) for the AA genotype and 2.6 (CI: 1.3-5.5, p=0.04) for the AG genotype. The risk is increased further by the status of two other chromosome 10 SNPs, rs10490924 and rs11200638.

rs4680 (Val158Met) is a well studied SNP in the COMT gene. spittoon summarizes them as *rs4680(A) = Met, more exploratory, lower enzymatic activity *rs4680(G) = Val, less exploratory, higher enzymatic activity Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compared with those with the Met substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergi...

rs4570625, also known as G-703T, is a SNP in the tryptophan hydroxylase 2 TPH2 gene. This SNP has been linked to several psychiatric and/or behavioural phenomena, including: * rs4570625 and rs4565946 linked to the pathogenesis of early-onset obsessive compulsive disorder * rs4570625 and rs11178997 in TPH2's regulatory region display preferential transmission * rs4570625(G;G) homozygosity was a significant predictor of clinical placebo response, being associated with greater improvement in anxiety symptoms. g2b2mh is rs4570625(G;G) is a significant predictor of clinical placebo response? maybe not panic disorder with a possible gender-dependent effect [omim:TRYPTOPHAN HYDROXYLASE 2; TPH2]

rs1024611, also known as the -2578A>G SNP due to its position in the promoter of the monocyte chemoattractant protein-1 MCP-1 CCL2 gene, influences the production of its corresponding protein, a chemokine involved in inflammatory responses. In a study focusing on 679 apparently healthy siblings of people with premature heart disease, investigators found that carriers of an rs1024611(C) allele - oriented as in dbSNP, not as published - independently predicted the risk of exercise induced ischemia in general. The odds ratio was reported to be 1.86 (CI: 1.14-3.04, p=0.014), regardless of race, age, sex and other factors. However, it is not clear if this risk carries over to individuals who lack siblings with heart disease. discussed in the spittoon as being relevant to HIV rs1024611 is not...

This SNP (C/T) is in 5' region of the HLA-C gene, 35 kb away from transcription initiation in or around the HLA-C gene. 'People with this tiny sequence variation, dubbed rs9264942, appear to have up to 90% less virus in their systems than those who carry other polymorphisms. About 10% of Europeans appear to carry two copies of rs9264942, which leads to an average 90% viral load reduction. About 50% of Europeans carry one copy, which gives a 60% reduction. By comparison, less than 40% of people of African descent appear to carry a single copy of the polymorphism.' Genetic variation may lower HIV load by 90% They are referring to the (C;C) genotype giving a 90% reduction and the (C;T) giving a 60% reduction. dbSNP page This SNP is also reported to account for 6.5% of the 15% variation in vir...

This SNP, in the ACTN3 gene, encodes a premature stop codon in a protein likely to be important in muscle function. The polymorphism alters position 577 of the alpha-actinin-3 protein, and while the most common nucleotide at this position, (C), encodes an arginine (amino acid code R), the stop codon is refered to as X. Hence, the SNP is referred to as R577X, with homozygotes being either RR or XX and heterozygotes being RX. The main report studying a relatively small number of Australian elite (ie ~Olympic) athletes found that, at least in females, the R allele (ie rs1815739(C)) is associated with sprinters, while the X allele (rs1815739(T)) is associated with endurance athletes. No female or Olympic-level sprinters were XX homozygotes (rs1815739(T;T)). The association tended the same way ...

rs1136287, also known as Met72Thr, is a SNP in the PEDF gene. Analysis of 86 Taiwanese Chinese patients with wet age related macular degeneration (ARMD) found the (T) allele to be more frequent in patients than in controls (50% vs 31%; p =.0005). The rs1136287(T;T) genotype was also more prevalent in patients than in controls (odds ratio 3.9, p = .0015).

rs6457617 has been reported in a large study to be associated with rheumatoid arthritis. This SNP is reported to be the most statistically significant of many SNPs similarly located in the MHC region. The risk allele (oriented to the dbSNP entry) is (T); the odds ratio associated with heterozygotes is 2.36 (CI 1.97-2.84), and for homozygotes, 5.21 (CI 4.31-6.30). [GWAS:Rheumatoid arthritis]

discussed in this blog post as possibly playing a role in coronary heart disease This SNP was also associated with increased risk for coronary artery disease in a Korean population. The association remained significant after adjusting for significant clinical covariates (P=0.001 to 0.024). We identified one risk haplotype (GGGG; P=0.017) and one protective haplotype (AAAA; P=0.007) for development of CAD. Further analysis suggested that the SNPs probably confer susceptibility to CAD in a dominance model (covariates-adjusted P=0.001 to 0.024; OR=2.37 to 1.54). Also found to be significant in a study of 416 Italian myocardial infarction patients. Found to be associated with coronary heart disease in a study of 1360 Chinese Han patients, with an odds ratio of 1.52 (CI: 1.13 - 2.04) for rs2383...

This SNP in TCF7L2 influences the risk of Type-2 diabetes (T2D). This SNP is also known as IVS3C>T. rs7903146(C;T) rs7903146(T;T) strongly predicted future type-2 diabetes. Considered in context with rs7903146 rs12255372 rs10885406. Note: this is one of two SNPs within the TCF7L2 gene that have been reported to be associated with type-2 diabetes, the other being rs4506565. They have approximately equal power to estimate risk for type-2 diabetes, and the results from one correlate 92% of the time with the other. Full text of the paper is available from from Plos Medicine. Or from NCBI as . TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. reconfirmed in a diverse population Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion...

rs3775291 is a SNP in the TLR3 gene associated with an amino acid change in the corresponding protein. In the orientation as shown in dbSNP, the more common rs3775291(G) allele encodes a leucine while the rarer rs3775291(A) allele encodes a phenylalanine. rs3775291 has been associated with one form of age related macular degeneration (ARMD), specifically, the form known as 'dry' ARMD, also known as geographic atrophy. A study of 3 case-control groups of Americans of European descent, comprising about 900 ARMD patients in total, indicated that having one rs3775291(A) allele reduces the odds of having dry ARMD about 30%, and being a rs3775291(A;A) homozygote cuts your odds by more than half. Specifically, the odds ratio of having dry ARMD with one minor allele is 0.712 (CI: 0.50-1.0), and fo...

This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent independently minor, but cumulatively significant, increased risk for breast cancer. For details of all 25 SNPs in this group, along with the two methods used to calculate overall risk estimates for breast cancer, refer to the SNPedia breast cancer entry. For this particular SNP, the risk (minor) allele is (C). The minor allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature. Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity ...

This SNP, along with SNPs rs660895 and rs3817964, is a tag SNP for the HLA-DRB1*0401 allele. The HLA-DRB1*0401 allele has been associated with higher risk for rheumatoid arthritis, and in particular, rheumatoid vasculitis. The association is seen particularly for individuals carrying two copies of, i.e. homozygous for, the allele. The reported odds ratio for rs6910071(G;G) homozygotes is 6.2 (CI: 1.01 - 37.9). The risk for rheumatoid arthritis may be higher for individuals carrying one copy (one 'dose') of the HLA-DRB1*0401 allele, if they also carry a different HLA-DRB1 risk allele. In particular, *0401/*0404 individuals are reported to have an odds ratio for rheumatoid vasculitis of 4.1 (CI: 1.1 - 16.2), and *0401/*0101 individuals have an odds ratio of 4.0 (CI: 1.4 - 11.6).

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. [omim:CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 2; CYP4F2] [GWAS:Acenocoumarol maintenance dosage]

rs572515 was the most significantly associated of a group of SNPs in the chromosome 1q32-33 region with risk for neovascular age related macular degeneration (p < 10-6).

rs1954787, located in an intron of the HTR2A 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

This SNP determines wet vs dry earwax as well as sweat production, it is also associated with lipid secretion it is commonly (T;T) for asians and (C;C) for europeans and africans. gnxp inidicates this snp influences risk of breast cancer [omim:ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 11; ABCC11]

rs9886784, a intergenic SNP on chromosome 9, is reported to influence the risk for Alzheimer's disease based on a study of ~1100 Canadian patients. THe risk allele is (A); the odds ratio is 3.23 (CI: 1.79 - 5.84).

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...

This SNP is in the TCF7L2 gene, and has been linked to type-2 diabetes, breast cancer and aggressive prostate cancer. This SNP is also known as IVS4G>T. is the paper which links it to Breast cancer. It suggests the T allele as increasing risk. reports the association of rs12255372 and rs7903146 with Type-2 diabetes in a Finnish sample. rs12255372 Common variants (rs12255372 and rs7903146) in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance Considered for type-2 diabetes with rs7903146 rs12255372 rs10885406. Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (p = 0.036). In a study of 1,457 prostate cancer case...

rs10494366, a SNP in the NOS1AP gene encoding the nitric oxide synthase I protein, accounts for some of the variation seen in abnormal heart rhythms, in particular, the QT interval. Based on studies totaling ~4,000 individuals of Caucasian ancestry, homozygotes for one allele have shorter QT intervals, while homozygotes for the other allele have a longer QT interval. A follow-up study determined that one rs10494366(G) allele was associated with a 3.8-ms (CI: 3.0 - 4.6ms, p=7.8x10(-20)) increase in QT interval duration, and two (G) alleles had twice that increase. No increase in risk for sudden death due to a cardiac problem was associated with this SNP, though. rs10494366 minor homozygotes had a 9.3 msec longer QT interval compared to major homozygotes (p=5.7x10(-5)); rs10918594 minor homo...

Along with rs6036025 serves as a proxy for rs1160312. related to baldness [omim:ALOPECIA, ANDROGENETIC, 3; AGA3]

rs1051730, also known as D398N, is a SNP in the nicotinic acetylcholine receptor alpha 3 subunit CHRNA3 gene. In two recent (2008) studies, together comprising over 6,000 lung cancer patients of European ancestry, the rs1051730(T) allele was very significiantly associated with increased risk. Having one copy (i.e. being a rs1051730(C;T) genotype) increased risk for lung cancer about 1.3x, and having two copies (rs1051730(T;T) individuals) represented 1.8x increased risk. Up to 14% of lung cancer incidence may be attributable to this allele. An independent study published at the same time concluded that (T) allele carriers for SNP rs1051730 are not at higher risk of becoming smokers compared to (C) carriers. However, if they do smoke, (T) carriers are quite likely to smoke more cigarettes t...

nature SNP rs1042725 is associated with height (P = 4E-8) in a study involving over 20,000 individuals. The gene harboring this SNP, HMGA2, is a strong biological candidate for having an influence on height, since rare, severe mutations in this gene are known to alter body size in mice and humans. rs1042725 is estimated to explain approx 0.3% of population variation in height in both adults and children (approx 0.4 cm increased adult height per C allele). rs1042725 is associated with increased height (0.36 cm 95% IC[0.12-0.61] per C allele, P=0.004). in men rs1042725 may explain 3% of height variability [omim:STATURE QUANTITATIVE TRAIT LOCUS 9; STQTL9] [GWAS:Height] [GWAS:Height]

This is basically a surrogate for rs7442295, and thus associated with higher serum urate levels. [omim:SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER]

This SNP, located in an intron of the BTBD9 gene, has a variant that is seen somewhat more frequently in individuals with restless legs syndrome. The risk allele is rs3923809(A); carriers of two such alleles, i.e. those with rs3923809(A;A) genotypes, are estimated to be 1.9 fold more likely to have restless legs syndrome than rs3923809(G;G) individuals. The authors of this study suggest that perhaps half of the cases of restless legs syndrome may involve the rs3923809 risk genotypes. Consistent with this finding, another report about rs3923809 links the (G) minor allele to a lower frequency of restless legs syndrome with an overall odds ratio of 0.57 (CI: 0.48-0.68). Note that 70-80% of all individuals in European populations carry one or two copies of the (A) major allele, yet restless le...

The (C) allele of rs6897932, located in the alternatively spliced exon 6 of IL7RA gene and encoding the amino acid threonine rather than isoleucine at amino acid position 244, is associated with a slight increase (18%) in risk of developing multiple sclerosis. [PMID 17660817; Nature Genetics 39, 1083 - 1091 (2007) SG Gregory et al.] Note that the (C) allele is the most common at this position in all known populations and influences the ratios of the alternative isoforms (membrane bound and soluble) of the gene. blog post giving perspective on the significance of this snp a significant risk factor for multiple sclerosis in four independent (overall P = 2.9 x 10(-7)) influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silenc...

CC linked to parkinson's disease We provide evidence for a novel, strong and reproducible association of the PITX3 promoter SNP rs3758549 : C>T (p=0.004) with PD. The C-allele appears to be a recessive risk allele with an estimated population frequency of 83%.

male-pattern baldness. Full text available. *G less likely to go bald before age 40 *A more likely to go bald before age 40

when used as part of gs122 this snp can influence male pattern baldness. Initial Sample Size: 578 cases, 547 controls Replication Sample Size: 1,351 cases, 2,485 controls Alopecia is readable, while the nature article is behind a paywall. This is one of the snps in gs122 [GWAS:Male-pattern baldness]

Along with rs201571 serves as a proxy for rs1160312. related to baldness

rs1385699, also known as Arg57Lys, is a SNP in the ectodysplasin A2 receptor EDAR2 gene. This gene is located on the X chromosome. The rs1385699(T) allele, which is the most common in European populations, was found to be associated with androgenetic alopecia in a case-control study of 400 males.

Several SNPs in the VKORC1 gene have been linked to warfarin sensitivity, with perhaps the most common being this SNP, rs9923231, also known as -1639G>A or VKORC1*2. Note that the orientation as published in scientific articles is typically on the opposite strand compared to the orientation in dbSNP. 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 demonstrate that VKORC1 promoter SNP a1639G>A (rs9923231), and the tightly linked intron1 SNP 1173C>T, predict warfarin dose more accurately than intron 2 SNP 1542G>C...

rs5400(T;T) carriers had a significantly higher intake of sugars blog discussion

rs2241880, a SNP in the ATG16L1 gene encoding a threonine to alanine substitution ('T300A') in a protein known to be involved in the function of the epithelial cells lining the intestine, has been associated with Crohn's disease in several recent studies. In another recent (2007) report, rs2241880 is confirmed to be associated with both Crohn's disease and ileal disease, but additionally, the authors calculate risk for individuals who are homozygotes for this SNP plus 2 others (in the IBD5 and NOD2 genes). Individuals homozygous for the risk alleles for all 3 of these SNPs are estimated to be at 20 fold higher risk (CI ~9-49) for Crohn's disease. From the largest most recent survey, the Crohn's disease-associated SNPs for IBD5 and NOD2 are, respectively, rs6596075 and rs17221417. associate...

Each G allele has been associated with an allelic odds ratio of 1.68 (p = 8.65 x 10(-18)) for risk of aggressive neuroblastoma. [omim:NEUROBLASTOMA]

rs4958847 is a SNP in the IRGM gene. A study of 507 CD patients, 475 UC patients and 576 controls from New Zealand Caucasians found that rs4958847, a SNP in the IRGM gene, was associated specifically with ileal Crohn's disease but not with other forms of inflammatory bowel disease. The reported odds ratio was 1.767, CI: 1.224-2.558, p=0.0022. Another study, including 557 Crohn's disease (CD) patients, 425 ulcerative colitis (UC) patients, and 672 ethnically matched Spanish controls as well as a meta-analysis concluded that rs4958847(A) was associated with CD (p=2.78 x 10(-17), pooled odds ratio 1.31) and UC (p=0.014, pooled odds ratio 1.13). [omim:IMMUNITY-RELATED GTPase FAMILY, M; IRGM]

[omim:PEPTIDE TRANSPORTER PSF2 POLYMORPHISM]

rs13387042(A;A) on has an estimated 1.44-fold greater risk than noncarriers, This initial association was later tested among patients in the Breast Cancer Association Consortium, including 31,510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35,969 controls. The association was confirmed for Caucasian women of European origin, with a per allele odds ratio of 1.12 (CI: 1.09-1.15). This association held regardless of ER or PR status. [omim:BREAST CANCER] [GWAS:Breast cancer] [GWAS:Breast cancer]