Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population

Saori Sakaue, Masato Akiyama, Makoto Hirata, Koichi Matsuda, Yoshinori Murakami, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada

Research output: Contribution to journalArticle

Abstract

The functional variants involved in alcohol metabolism, the A allele of rs1229984:A > G in ADH1B and the A allele of rs671:G > A in ALDH2, are specifically prevalent among East Asian population. They are shown to be under recent positive selection, but the reasons for the selection are unknown. To test whether these positively selected variants have beneficial effects on survival in modern population, we performed the survival analyses using the large-scale Japanese cohort (n = 135,974) with genotype and follow-up survival data. The rs671-A allele was significantly associated with the better survival in the additive model (HR for mortality = 0.960, P = 1.7 × 10−5), and the rs1229984-A had both additive and non-additive effects (HR = 0.962, P = 0.0016 and HR = 0.958, P = 0.0066, respectively), which was consistent with the positive selection. The favorable effects of these alleles on survival were independent of the habit of alcohol consumption itself. The heterogenous combinatory effect between rs1229984 and rs671 genotype was also observed (HRs for AA genotype at rs671 were 1.03, 0.80, and 0.90 for GG, GA, and AA genotype at rs1229984, respectively), supposedly reflecting the synergistic effects on survival.

Original languageEnglish
JournalEuropean Journal of Human Genetics
DOIs
Publication statusAccepted/In press - 01-01-2019

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Alleles
Genotype
Mortality
Population
Survival Analysis
Alcohol Drinking
Habits
Alcohols

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Sakaue, Saori ; Akiyama, Masato ; Hirata, Makoto ; Matsuda, Koichi ; Murakami, Yoshinori ; Kubo, Michiaki ; Kamatani, Yoichiro ; Okada, Yukinori. / Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population. In: European Journal of Human Genetics. 2019.
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Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population. / Sakaue, Saori; Akiyama, Masato; Hirata, Makoto; Matsuda, Koichi; Murakami, Yoshinori; Kubo, Michiaki; Kamatani, Yoichiro; Okada, Yukinori.

In: European Journal of Human Genetics, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population

AU - Sakaue, Saori

AU - Akiyama, Masato

AU - Hirata, Makoto

AU - Matsuda, Koichi

AU - Murakami, Yoshinori

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

AU - Okada, Yukinori

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