Genome-wide association meta-analysis and Mendelian randomization analysis confirm ALDH2 influencing on sleep duration in the Japanese population

Sleep
Takeshi NishiyamaSadao Suzuki

Abstract

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 has been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31,230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (P-value < 5.0×10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5,140 Japanese individuals (P-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking fr...Continue Reading

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Citations

Sep 24, 2020·Journal of Epidemiology·Kenji TakeuchiKenji Wakai
Jul 1, 2021·Cardiology and Therapy·Lyudmila Korostovtseva
Aug 27, 2021·European Journal of Clinical Investigation·Minhan YiYuan Zhang
Jun 9, 2021·Annual Review of Nutrition·Hassan S Dashti, José M Ordovás

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