rs234715

mixedMag 3.0

This is a intron variant variant in the CBS gene.

Key Literature Trait Associations

Homocysteine Metabolism

rs234715 is an intronic variant in CBS, which encodes cystathionine beta-synthase, the enzyme catalyzing the first step of the transsulfuration pathway that converts homocysteine to cystathionine. CBS variants are in strong linkage disequilibrium across the locus; common CBS haplotypes have not shown consistent independent effects on fasting homocysteine levels in healthy populations.

van Meurs JB et al. “Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.” The American Journal of Clinical Nutrition 98(3):668-76 (2013)

Allele T

OR —

p 5.0e-8

N 44,147

Small GWAS

European

De Stefano V et al. “Linkage disequilibrium at the cystathionine beta synthase (CBS) locus and the association between genetic variation at the CBS locus and plasma levels of homocysteine. The Ears II Group. European Atherosclerosis Research Study.” Annals of Human Genetics 62(6):481-490 (1998)

Allele T

OR —

p —

Candidate gene study

Williams SR et al. “Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke.” Plos Genetics 10(3):e1004214 (2014)

Allele T

OR —

p 3.2e-26

N 4,810

Meta-analysis

European

Tsai MY et al. “Polygenic association with total homocysteine in the post-folic acid fortification era: the CARDIA study.” Molecular Genetics and Metabolism (2009)

Allele T

OR —

p —

N 1,689

Preliminary work

multi-ancestry (European and African American)

Yakub M et al. “Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population.” Plos One (2012)

Allele T

OR 0.58

p 4.7e-2

N 872

Preliminary work

Pakistani

Kluijtmans LA et al. “Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults.” Blood (2003)

Allele T

OR —

p —

N 452

Candidate gene study

European (Northern Irish)

Autism spectrum disorder

A single gene-environment interaction study (n=707) found that mothers carrying the CBS rs234715 GT or TT genotype who did not take periconceptional prenatal vitamins had significantly elevated odds of having a child with autism (OR=2.6, 95% CI 1.2–5.4). The effect was specific to the absence of prenatal vitamins and was not observed in vitamin-taking mothers, suggesting that folate/B-vitamin supplementation may mitigate the risk conferred by reduced CBS-mediated homocysteine clearance in vulnerable pregnancies. This interaction finding has not been independently replicated and should be considered hypothesis-generating.

Schmidt RJ et al. “Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism.” Epidemiology (cambridge, Mass.) (2011)

Allele T

OR 2.60

p —

N 707

Preliminary work

multi-ancestry (California cohort)

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ClinVar annotation

Benign★★★☆

2 submitters1 publication

View on ClinVar →

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Research that mentions this SNP (1)

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Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome

AssociationN=243Adam E. Locke et al.(2010)· Genetic Epidemiology

This case-control study examined folate pathway gene variants in 121 DS-AVSD cases and 122 DS controls (no CHD). Tag SNPs in MTHFR, MTR, MTRR, CBS, and SLC19A1 were genotyped. SLC19A1 showed significant gene-level association with atrioventricular septal defect (P=0.01), with multiple tag SNPs nominally associated (OR 1.08-1.72). All significant SLC19A1 SNPs showed strong LD (r²≥0.80) with the nonsynonymous variant rs1051266 (c.80A>G, p.H27R). MTHFR c.1298A was over-transmitted to cases (P=0.05) and under-transmitted to controls (P=0.02), showing association in FBAT analysis (P=0.03 dominant, P=0.01 additive). These results suggest folate pathway disruption contributes to AVSD risk in Down syndrome individuals.

Traits studied:Atrioventricular septal defect (AVSD)Congenital heart defectsDown syndrome

rs234715

Key Literature Trait Associations

Homocysteine Metabolism

Autism spectrum disorder

ClinVar annotation

Research that mentions this SNP (1)

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