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

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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
Pages (from-to)378-382
Number of pages5
JournalEuropean Journal of Human Genetics
Volume28
Issue number3
DOIs
Publication statusPublished - 01-03-2020

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Sakaue, S., Akiyama, M., Hirata, M., Matsuda, K., Murakami, Y., Kubo, M., Kamatani, Y., & Okada, Y. (2020). Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population. European Journal of Human Genetics, 28(3), 378-382. https://doi.org/10.1038/s41431-019-0518-y