A Candidate Gene Association Study of Alcohol Consumption in Young Women*

Abstract

Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1,014 single-nucleotide polymorphisms in genes related to addiction. Data were drawn from the Missouri Adolescent Female Twin Study (MOAFTS) with replication in the college drinking sample (CDS). Genotypic and phenotypic data were available on 827 MOAFTS and 100 CDS women of European-American ancestry. Data on 1,014 single-nucleotide polymorphisms (SNPs) across 130 genes related to addiction were utilized. Association was conducted in QTDT, which allows for identity-by-descent information to account accurately for twin status in the analysis. The total association variance components model was used, with specification of variance components for relatedness in MOAFTS. The top signals included clusters of SNPs in tryptophan hydroxylase 2 (TPH2) (e.g., rs1386496, p = 0.0003) and dopa decarboxylase (DDC) (e.g., rs3779084, p = 0.0008), genes that encode proteins responsible for serotonin synthesis. Additional polymorphisms in ADH1B, ADH1C, ADH7, and ADH1A1 were also associated at p < 0.05. The false discovery rate for the top signal (p = 0.0003) was 0.15, suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C. While no results survive the burden of multiple testing, nominal findings in TPH2 and DDC suggest the potential role of the serotonin synthesis pathway in alcohol consumption.