Journal
SLEEP
Volume 42, Issue 6, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/sleep/zsz046
Keywords
usual sleep duration; alcohol consumption; genome-wide association study; Mendelian randomization
Categories
Funding
- JSPS KAKENHI [26293143, 15K06915]
- Suzuken Memorial Foundation
- Biobank Japan Project - Ministry of Education, Culture, Sports, Sciences and Technology Japan
- Japan Agency for Medical Research and Development
- National Cancer Research and Development Fund from 2010
- Ministry of Health, Labour and Welfare of Japan
- JSPS KAKENHI from the Japan Ministry of Education, Science, Sports, Culture and Technology [16H06277]
- National Cancer Center Research and Development Fund [29-A-2]
- Ministry of Education, Culture, Sports, Sciences and Technology Japan
- [17015018]
- [221S0001]
- Grants-in-Aid for Scientific Research [26293143, 15K06915] Funding Source: KAKEN
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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 have 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 x 10(-8)). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 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 (r(G) = 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 frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.
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