Journal Article

A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks

Kapoor, Manav, Rice, John, Bierut, Laura, Foroud, Tatiana, Porjesz, Bernice, Edenberg, Howard J., Goate, Alison, Nurnberger, John I., Bertelsen, Sarah, Agrawal, Arpana, Saccone, Nancy, Hesselbrock, Victor, Hinrichs, Anthony L., Bucholz, Kathleen, Kramer, John, Tischfield, Jay, Dick, Danielle, Wang, Jen-Chyong, Wetherill, Leah, Le, Nhung, Budde, John, Schuckit, Marc, Harari, Oscar

2013

Overview

Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families ( N  = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case–control sample ( N  = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 ( p  = 2.1 × 10 −6 ) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 ( p  = 7.1 × 10 −7 ), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 ( p  = 7.2 × 10 −7 ) and PLCL1 genes ( p  = 4.1 × 10 −6 ) with maxdrinks. A variant in AUTS2 and variants in INADL , C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset ( p  ≤ 10 −4 ) far more showed the same direction of effect in the other dataset than would be expected by chance ( p  = 2 × 10 −3 , 3 × 10 −6 ), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Addiction / Adult / Alcohol Drinking - genetics / Alcoholic beverages / Alcoholism / Alcoholism - genetics / Biomedical and Life Sciences / Biomedicine / Cancer / Chromosomes / Chromosomes, Human, Pair 13 - genetics / Collaboration / Datasets / DNA-Binding Proteins - genetics / Drinking of alcoholic beverages / Female / Gene Function / Gene-Environment Interaction / Genes / Genetic Loci / Genetic Predisposition to Disease / Genetics / Genetics, Population - methods / Genome, Human / Genome-Wide Association Study / Genomes / Genomics / Human Genetics / Humans / LIM Domain Proteins - genetics / Male / Medicine / Meta-analysis / Metabolic Diseases / Middle Aged / Molecular Medicine / Original Investigation / Pedigree / Phenotype / Phosphoinositide Phospholipase C - genetics / Polymorphism, Single Nucleotide / Transcription Factors - genetics