title: 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.
authors: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA; Department of Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors: Yue
authors: Y
authors: Pan
authors: Xingguang
authors: X
authors: Luo
authors: Xuefeng
authors: X
authors: Liu
authors: Long-Yang
authors: LY
authors: Wu
authors: Qunyuan
authors: Q
authors: Zhang
authors: Liang
authors: L
authors: Wang
authors: Weize
authors: W
authors: Wang
authors: Lingjun
authors: L
authors: Zuo
authors: Ke-Sheng
authors: KS
authors: Wang
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000235:genetics*; D001315:Australia; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics; D018672:Community Health Planning; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics; D044465:White People / Q000235:genetics
keywords: DDC; DTWD2; Genome-wide association; KCNB2; Maximum number of drinks; Meta-analysis; NDST4; SGOL1
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