Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS, and impact on esophageal cancer risk in Japanese people

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 of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-r..., We performed an rs671 genotype-stratified GWAS meta-analysis of alcohol consumption within six Japanese cohorts. To validate the stratified approach, we applied a joint meta-analysis (JMA). Further, to validate the impact of the discovered loci on alcohol-related disease, we performed a meta-analysis of two esophageal cancer case-control studies. 
GWAS meta-analysis
Study subjects and genotyping: We performed a genome-wide meta-analysis based on the Japanese Consortium of Genetic Epidemiology studies (J-CGE) (1), the Nagahama Study (2), and the BBJ Study (3,4). The J-CGE consisted of the following Japanese population-based and hospital-based studies: the HERPACC Study (5), the J-MICC Study (6,7), the JPHC Study (8), and the TMM Study (9). Individual study descriptions and an overview of the characteristics of the study populations are provided in the Supplementary Information and table S1. Data and sample collection for the participating cohorts were approved by the respective research ..., No special software are required to open the files., # Title of Dataset

Full summary statistics of GWAS meta-analysis and JMA for daily alcohol intake and drinking status, alongside aggregated data from individual studies for GWAS, JMA, and esophageal cancer case-control study

We performed an rs671 genotype-stratified GWAS meta-analysis of alcohol consumption based on the Japanese Consortium of Genetic Epidemiology studies (J-CGE), the Nagahama Study, and the BBJ Study. The J-CGE consisted of the following Japanese population-based and hospital-based studies: the HERPACC Study, the J-MICC Study, the JPHC Study, and the TMM Study. Individual study descriptions and an overview of the characteristics of the study populations are provided in the Supplementary Information and table S1. To validate the stratified approach, we applied a joint meta-analysis (JMA). Further, to validate the impact of the discovered loci on alcohol-related disease, we performed a meta-analysis of two esophageal cancer case-control studies within the HERPACC Study ...