Genotype-stratified GWAS meta-analysis reveals novel loci associated with alcohol consumption
Koyanagi, Y. N.; Nakatochi, M.; Ito, H.; Kasugai, Y.; Narita, A.; Kawaguchi, T.; Ikezaki, H.; Hishida, A.; Hara, M.; Takezaki, T.; Koyama, T.; Mikami, H.; Suzuki, S.; Katsuura-Kamano, S.; Kuriki, K.; Nakamura, Y.; Takeuchi, K.; Hozawa, A.; Kinoshita, K.; Sutoh, Y.; Tanno, K.; Shimizu, A.; Oze, I.; Kawakatsu, Y.; Taniyama, Y.; Imoto, I.; Tabara, Y.; Takahashi, M.; Setoh, K.; Suzuki, S.; Goto, A.; Katagiri, R.; Yamaji, T.; Sawada, N.; Tsugane, S.; Wakai, K.; Yamamoto, M.; Sasaki, M.; Matsuda, F.; Iwasaki, M.; Brennan, P.; Matsuo, K.
Show abstract
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.
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