Genome-wide association studies of maximum number of drinks

Abstract

Maximum number of drinks (MaxDrinks) defined as "Maximum number of alcoholic drinks consumed in a 24-h period" is an intermediate phenotype that is closely related to alcohol dependence (AD). Family, twin and adoption studies have shown that the heritability of MaxDrinks is approximately 0.5. We conducted the first genome-wide association (GWA) study and meta-analysis of MaxDrinks as a continuous phenotype. 1059 individuals were from the Collaborative Study on the Genetics of Alcoholism (COGA) sample and 1628 individuals were from the Study of Addiction - Genetics and Environment (SAGE) sample. Family sample with 3137 individuals was from the Australian twin-family study of alcohol use disorder (OZALC). Two population-based Caucasian samples (COGA and SAGE) with 1 million single-nucleotide polymorphisms (SNPs) were used for gene discovery and one family-based Caucasian sample was used for replication. Through meta-analysis we identified 162 SNPs associated with MaxDirnks (p < 10(-4)). The most significant association with MaxDrinks was observed with SNP rs11128951 (p = 4.27 × 10(-8)) near SGOL1 gene at 3p24.3. Furthermore, several SNPs (rs17144687 near DTWD2, rs12108602 near NDST4, and rs2128158 in KCNB2) showed significant associations with MaxDrinks (p < 5 × 10(-7)) in the meta-analysis. Especially, 8 SNPs in DDC gene showed significant associations with MaxDrinks (p < 5 × 10(-7)) in the SAGE sample. Several flanking SNPs in above genes/regions were confirmed in the OZALC family sample. In conclusions, we identified several genes/regions associated with MaxDrinks. These findings can improve the understanding about the pathogenesis of alcohol consumption phenotypes and alcohol-related disorders.

Keywords: DDC; DTWD2; Genome-wide association; KCNB2; Maximum number of drinks; Meta-analysis; NDST4; SGOL1.