Genotype-stratified GWAS meta-analysis reveals novel loci associated with alcohol consumption

An East Asian-specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis in up to 40,679 individuals from Japanese populations to uncover additional loci associated with alcohol consumption in an rs671-dependent manner. No loci satisfied the genome-wide significance threshold in wild-type homozygotes (GG), but six loci ( ADH1B, ALDH1B1, ALDH1A1, ALDH2, GOT2 , and MYOM1-MYL12A ) did so in heterozygotes (GA). Of these, three loci ( ALDH2, GOT2 , and MYOM1-MYL12A ) were novel, and two ( ADH1B and ALDH1B1 ) showed genome-wide significant interaction with rs671. Our results identify a new genetic architecture associated with alcohol consumption, and shed additional light on the genetic characteristics of alcohol consumption among East Asians.