Promethease Report

Note that this SNP is unusual in at least two regards. First, it is defined in both dbSNP and here in SNPedia (currently at least) as being on the minus strand, even though the vast majority of its fellow CYP21A2 gene SNPs are defined on the plus strand. The literature and most (other) databases define this SNP based on the plus strand. Second, there are three alleles for this SNP; as defined on the minus strand, there are plenty of individuals walking around with rs6467(G) and rs6467(T) alleles, both of which lead to fully functional 21-hydroxylase (the enzyme encoded by the CYP21A2 gene), and there are also some individuals carrying a rs6467(C) allele, which severely reduces enzyme activity. The rs6467(T) polymorphism defines the CYP21A2*1B allele according to the CYP21A2 Nomenclature ta...

This SNP, located in the PTPN22 gene and also known as R620W, or 1858C>T, may influence Rheumatoid Arthritis and other autoimmune diseases, including but not limited to, multiple sclerosis, Crohn's disease, celiac disease and type-1 diabetes. In an expanded follow-up study of >6,000 controls and 6,000 patients, the heterozygote odds ratio for type-1 diabetes for this SNP was recalculated to be 1.98 (CI 1.82-2.15). rs2476601 was confirmed in another 2007 study to be a risk factor for RA . * confirms the association of rs2476601 rheumatoid arthritis * two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA * see rs2476601(A;G) * * * * * rs2476601 shows a 0.75 (r squared) correlation with rs6679677, a SNP in the RSBN1 gene associated with rheumatoid arthritis...

rs800292 is a SNP in the complement factor H CFH gene; it has been linked to blindness in age related macular degeneration. This SNP is also known as 184G>A, I62V, or Val62Ile. A haplotype of rs1061170 rs3753394 rs800292 rs1329428 (TGTC) was found to confer a significantly increased likelihood of exudative AMD CFH variations appear to contribute to ARMD in Caucasians, but not in Japanese A study of Chinese AMD patients reports that carriers of both rs11200638 and rs800292 risk alleles pushes the odds ratio for AMD up to 23x. Overall, an 'extremely high' population attributable risk (PAR) of 78% reported for these SNPs. rs800292 was associated with polypoidal choroidal vasculopathy (PCV) in a study of 130 Japanese patients. age related macular degeneration Susceptibility genes for age-re...

rs5888 is a SNP in the scavenger receptor class B, member 1 SCARB1 gene. In a case-control study of two Caucasian populations totaling 2,498 patients, rs5888(C;T) heterozygotes had an increased odds ratio of 2.9 (CI: 1.6-5.3, p<0.002) for age-related macular degeneration (ARMD) based on a pooled analysis. Subgroup analysis indicated that the odds ratio for exudative forms of ARMD was even higher (3.6; CI: 1.7-7.6, p>0.0015) for rs5888(C;T) heterozygotes.

rs1061170 is a SNP in the complement factor H CFH gene; it is also known as Tyr402His. The rs1061170(T) allele encodes the more common Tyr (Y), while the generally rarer rs1061170(C) encodes the His (H). This SNP has been associated primarily with age related macular degeneration, and to a lesser extent, with longevity. This research paper shows that CFH Y402H is the relevant mutation. A haplotype of rs1061170 rs3753394 rs800292 rs1329428 (TGTC) was found to confer a significantly increased likelihood of exudative AMD. rs1061170 (aka Y402H 1277 T>C) was not associated with exudative AMD. CFH variations appear to contribute to ARMD in Caucasians, but not in Japanese CFH variant rs1061170 Y402H is strongly associated with both dry and wet AMD rs1061170(C) alleles are significantly associa...

rs5963409 is a SNP in the ornithine carbamoyltransferase OTC gene; this SNP is also known as the -389 G/A SNP. Previous association studies were extended to a population of 2113 Alzheimer's disease cases and 1580 controls from northern France, western France, the United Kingdom and Italy. The rs5963409(A) minor allele was weakly but significantly associated with an increased risk of developing Alzheimer's disease (odds ratio 1.19, p = 0.004). This association was independent of age and ApoE status.

rs2160525 is in linkage disequilibrium with a polymorphism that increases susceptibility to late-onset Alzheimer's disease (LOAD) 1.30 times for carriers of the G allele.

[GWAS:Alzheimer's Disease]

The risk allele is T (in dbSNP orientation), according to a table published by the National Human Genome Research Institute. [GWAS:Alzheimer's disease]

This SNP, a synonymous substitution in the ABCA2 gene, has been linked to early onset Alzheimer's disease with an odds ratio of 3.8 for disease development in carriers of the A allele (in dbSNP orientation) compared to controls (95% CI 2-7.3), based on a study of ~400 Caucasian patients. Subsequently, this association was replicated in a Western European population (n=291, p=0.008), but not in a second sample from Southern Europe. rs908832 was not polymorphic in a Japanese sample. Furthermore, rs908832 was not associated with either serum cholesterol levels or with the risk for coronary artery disease, but did seem to be related to cholesterol levels in the cerebrospinal fluid. [OMIM:ATP-BINDING CASSETTE, SUBFAMILY A, MEMBER 2; ABCA2]

rs6690993 is one of 6 SNPs found upstream of an (uncharacterized) gene known as FLJ10986 that have been found to be overrepresented in patients with sporadic amyotrophic lateral sclerosis (ALS). A genome-wide association study of 1,152 ALS patients determined an allelic odds ratio of 1.35 for the rs6690993(G) allele (CI: 1.13-1.62, p=3x10^-4). This association was seen only in Caucasians upon replication and not in non-Caucasians. The genotypic odds ratio presented were 1.69 (CI: 1.16-2.47) and 1.2 (CI: 0.81-1.71) for homozygotes and heterozygotes, respectively. * Note: this SNP is in strong linkage disequilibrium with rs6700125 (r²>0.8) A study involving a large case-control series from the Netherlands, Belgium, Sweden and Ireland (total: 18...

rs6700125 is one of 6 SNPs found upstream of an (uncharacterized) gene known as FLJ10986 that have been found to be overrepresented in patients with sporadic amyotrophic lateral sclerosis (ALS). A genome-wide association study of 1,152 ALS patients determined an allelic odds ratio of 1.38 for the rs6700125(T) allele (CI: 1.16-1.65, p=0.00032). The genotypic odds ratio presented were 1.76 (CI: 1.22-2.55) and 1.2 (CI: 0.83-1.73) for homozygotes and heterozygotes, respectively. * Note: this SNP is in strong linkage disequilibrium with rs6690993 (r²>0.8) A study involving a large case-control series from the Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls) found no significant association between sporadic ALS and the six p...

[GWAS:Amyotrophic lateral sclerosis]

rs3849942 is one of 2 SNPs from the ch 9p21.2 region associated in a large GWAS study with ALS risk, the other SNP being rs2814707. In this study, the reported odds ratio for rs3849942(A) was 1.22 (CI: 1.15 - 1.30, p = 4.64 x 10e-10). The odds ratio for the minor rs3849942(A) allele was 1.15 (p=1.01x10e-8). From a study of 405 Finnish patients with ALS, rs3849942 was found within a 42 SNP haplotype associated with highly increased (p = 7 x 10e-33) risk when patients with familial ALS were compared to controls (odds ratio of 21.0, CI: 11.2-39.1). This haplotype overlapped with a region reported (by others) to associate with risk for frontotemporal dementia. In terms of population attributable risk, for the 93 patients with familial ALS, this 9p21 locus accounts for 38% and that of rs1304801...

rs6539137 is one of several TXNRD1 SNPs significantly associated with familial amyotrophic lateral sclerosis (FALS) but not sporadic amyotrophic lateral sclerosis (ALS). The risk allele, rs6539137(A), is also associated with an earlier age of onset by 8 years, and the shift was more significant in males (in fact, insignificant in females).

rs4630362 is one of several TXNRD1 SNPs significantly associated with familial amyotrophic lateral sclerosis (FALS) but not sporadic amyotrophic lateral sclerosis (ALS).

23andMe blog aneurysm *rs700651 2 G 1.18x risk 1.56x risk *rs10958409 8 A 1.37x risk 1.79x risk *rs1333040 9 T 1.29x risk 1.67x risk Increased risk of intracranial (brain aneurysm) with certain SNPs. rs700651(G;G) associated with 1.56x risk of developing an intracranial aneurysm (IA). Heterozygote risk is 1.18x. Other SNPs associated with increased risk of developing IA include rs1333040 and rs10958409. rs10958409 is located on chromosome 9; rs1333040 is located on chromosome 8; rs700651 is located on chromosome 2. Unfortunately, the first sign of an intracranial aneurysm is rupture. Catastrophic bleeding and death may result. Specific knowledge of risk may influence screening decision. More information: Intracranial aneurysm screening: indications and advice for practice. . [PharmGKB:Non...

rs30187 is one of several SNPs in the ERAP1 gene that has been shown in a large (over 1,000 Caucasian patients) study to be associated with ankylosing spondylitis. Each T allele appears to increase the odds by about 1.4x (p=3.4x10e-10). A study of 872 Korean patients found that each T allele was associated with 1.5x higher odds of ankylosing spondylitis. [GWAS:None]

rs10818488, a SNP located in between the C5 and TRAF1 genes, was identified as the SNP from this region showing maximal association with rheumatoid arthritis in a study of ~2000 Dutch, Swedish, and American patients. This study also reported that this SNP was significantly (p = 0.008) associated with increased disease progression as determined by radiographic damage over time in rheumatoid arthritis patients. The risk allele for rs10818488 is the minor allele, (A). If (and as) reported from just the Dutch RA patients, the odds ratio associated with rs10818488(A;G) heterozygotes is 1.38 (CI 1.04-1.83, p = 0.027) and with rs10818488(A;A) homozygotes 2.06 (95% CI 1.42-2.98, p = 1.29E-3). Combining data from all 2,000 patients, the odds ratio associated with rs10818488(A) is 1.26 (CI 1.15-1.37...

rs5067 is a SNP in the natriuretic peptide precursor A NPPA gene. In a study of ~500 asthma patients, rs5067(G) were at reduced (50% or 76%) risk; the odds ratio in the first and second populations were 0.5 (CI: 0.29-0.84, p=0.009) and 0.24 (CI: 0.11-0.53, p<0.0001), respectively. The population-attributable risk for asthma in carriers of the rs5067(G) allele was 23.3%.

rs37973 is a SNP in the promoter region of the glucocorticoid induced transcript 1 GLCCI1 gene on chromosome 7. Based on 4 populations totaling 900+ asthma patients, the rs37973(G) allele was associated (p = 0.0007, pooled data) with lower amounts of improvement of lung function in response to inhaled glucocorticoids such as budesonide. The mean (±SE) increase in forced expiratory volume in 1 second (FEV1) in treated rs37973(G;G) patients was about one third of that seen in rs37973(A;A) patients (3.2±1.6% vs. 9.4±1.1%). Based on dividing the response into highest vs lowest quartiles of response, the allelic odds ratio of falling into the lowest responding quartile based on an additive genetic model was calculated to be 1.52 (CI: 1.13 - 2.03). Genotype accounted for about 7% ...

Atopic Dermatitis

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...

[PharmGKB:Non-Curated GWAS results: Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. (Initial Sample Size: 938 affected trios; Replication Sample Size: NR); (Region: 2q33.1; Reported Gene(s): FLJ39061, FZD7; Risk Allele: rs1521882-A); (p-value= 0.000008).This variant is associated with Attention-deficit/hyperactivity disorder and conduct disorder.] [GWAS:Attention-deficit/hyperactivity disorder and conduct disorder]

T allele associated with better response to treatment of ADHD with atomoxetine.

[PharmGKB:Non-Curated GWAS results: Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. (Initial Sample Size: 938 affected trios; Replication Sample Size: NR); (Region: 12q21.2; Reported Gene(s): PAWR; Risk Allele: rs7297018-A); (p-value= 0.000004).This variant is associated with Attention-deficit/hyperactivity disorder and conduct disorder.] [GWAS:Attention-deficit/hyperactivity disorder and conduct disorder]

rs3923890 has been reported to be a SNP potentially associated with increased risk for autism

A study of 151 Korean families reported that the rs2745557(A) allele of the PTGS2 gene, also known as cyclooxygenase-2 (Cox-2), was overtransmitted (p<0.01) in autism spectrum disorders.

nature The inheritance of the AC haplotype of rs1861972 – rs1861973, the C allele of rs1811399, and the C allele of rs1234747 may contribute to autism by affecting microRNA rs1861972(A) + rs1861973(C) haplotype assoc. with '''protective''' effect against autism in a study of 818 Han Chinese (184 diag. autistics, 225 unrelated volunteers, 409 randomly selected) [OMIM:ENGRAILED 2; EN2]

rs3135391 is highly correlated with the HLA-DRB1*1501 allele. The risk allele (T), is associated with a 3 to 6 fold higher risk for developing multiple sclerosis, and is the most significantly associated risk factor for MS. [PMC2892470] In one study, for example, the odds ratio was reported to be 3.04 (p < 1 x 10e-78). The HLA-DRB1*1501 allele has also been associated with other autoimmune diseases, such as systemic lupus erythematosis (SLE) (see) and possibly narcolepsy. The HLA-DRB1*1501 allele is fairly common; for example, it occurs in 15-30% of individuals of Northern European ancestry. [PMC2892470] An interesting series of correlations have been woven together to suggest that a possible way to lower the risk of rs3135388(T) carriers developing multiple sclerosis would be to ensure...

This is the 23andWe discovery: 'Male Pattern Baldness: Preliminary Research'. It affects appearance.

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

nature Baldness OR = 1.60, P = 1.1 times 10-14). see also gs122 The risk allele is assumed to be rs1160312(A). Note that a haplotype consisting of rs201571(T) - rs6036025(G) has a perfect correlation (r2 = 1) with rs1160312(A), at least in the Caucasian population studied. [PharmGKB:Non-Curated Male-pattern baldness susceptibility locus at 20p11. (Initial Sample Size: 578 cases, 547 controls; Replication Sample Size: 1,351 cases, 2,485 controls); (Region: 20p11.22; Reported Gene: PAX1; Risk Allele: rs1160312-A) This variant is associated with Male-pattern baldness.] [OMIM:ALOPECIA, ANDROGENETIC, 3; AGA3] [GWAS:Male-pattern baldness]

This SNP, located in the PTPN22 gene and also known as R620W, or 1858C>T, may influence Rheumatoid Arthritis and other autoimmune diseases, including but not limited to, multiple sclerosis, Crohn's disease, celiac disease and type-1 diabetes. In an expanded follow-up study of >6,000 controls and 6,000 patients, the heterozygote odds ratio for type-1 diabetes for this SNP was recalculated to be 1.98 (CI 1.82-2.15). rs2476601 was confirmed in another 2007 study to be a risk factor for RA . * confirms the association of rs2476601 rheumatoid arthritis * two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA * see rs2476601(A;G) * * * * * rs2476601 shows a 0.75 (r squared) correlation with rs6679677, a SNP in the RSBN1 gene associated with rheumatoid arthritis...

Linked to bipolar disorder in one of the most comprehensive studies in 2007. Risk allele with reference to dbSNP orientation is reported to be (T), with either one or two copies leading to an odds ratio of 2 (CI 1.6-2.7). Some replications, but in 2011 23andMe published as failed to replicate in Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment. Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort. Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies. [PharmGKB:Non-Curated GWAS Results: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls (Initial Sample...

rs1375144, a SNP in the DPP10 gene, has been reported in a large study to be associated with bipolar disorder. The risk allele (oriented to the dbSNP entry) is (T); the odds ratio associated with heterozygotes is 1.32 (CI 1.07-1.63), and for homozygotes, 1.59 (CI 1.29-1.96). Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort. [GWAS:None]

rs2609653 has been reported in a large study to be associated with bipolar disorder. The risk allele (oriented to the dbSNP entry) is (C); the odds ratio associated with heterozygotes is 1.43 (CI 1.19-1.71), and for homozygotes, 3.62 (CI 1.26-10.44). [GWAS:None]

[GWAS:Bipolar disorder]

rs1156044(A) was significantly associated with bipolar disorder (p = 0.013) but differed in allele (rs1156044 G allele) from that previously reported as associated with BD.

[GWAS:Bipolar disorder]

[GWAS:Bipolar disorder]

rs5275, also known as exon1-+837T>C, is a SNP in the PTGS2 gene. A study of 635 Caucasian bladder cancer patients found a reduced risk associated with the minor (C) allele of rs5275, (odds ratio 0.68, CI: 0.54-0.87, p=0.002, remaining significant after multiple comparison adjustment). (T;T) genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better survival when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in colorectal cancer Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma. Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism. Cyclooxygenase-2 polymorphisms in Parkinso...

Each G allele is associated with 0.89 x odds of high blood pressure, according to 23andMe. 23andMe blog blood pressure High Blood Pressure (Hypertension) [GWAS:Systolic blood pressure]

A study of ~15,000 Europeans found that increased circulating natriuretic peptide and thus lower blood pressure and hypertension were associated with SNPs rs17376328(A), rs5068, rs198358(C), rs632793(G) 23andMe blog Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting. Dissecting complex traits: recent advances in hypertension genomics. Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study. Association of common variants in NPPA and NPPB with blood pressure does not translate into kidney damage in a general population study. Association of genetic variation in the natriuretic peptide system with...

diastolic blood pressure [PharmGKB:Non-Curated GWAS results: Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness (Initial Sample Size: 644-1,327 individuals, depending on measure (Framingham); Replication Sample Size: NR). This variant is associated with Blood pressure.] [GWAS:Blood pressure]

diastolic blood pressure [GWAS:Blood pressure]

rs3184504 is a nonsynonymous SNP in the SH2B3 gene, and it is also known as R262W. In a recent (2008) study of non-HLA SNP associations of 1600+ celiac disease patients, this SNP was considered one of the most significant. The odds ratio for the minor allele was 1.19 (CI:1.10-1.30, p=1.33x10e-7). rs653178, another SNP in strong linkage disequilibrium (r²>0.99) with rs3184504, was also associated with celiac disease. associated with type-1 diabetes 23andMe blog coronary artery disease and heart attack SNP Risk Version Effect *rs646776 T 1.19 *rs17465637 C 1.14 *rs1746048 C 1.17 *rs6725887 C 1.17 *rs11206510 T 1.15 *rs3184504 T 1.13 *rs2306374 C 1.15 *rs3782886 C 1.44 23andMe blog blood pressure Pharmacogenetic implications for eight common blood pressure-associated...