| Literature DB >> 30810208 |
Takeshi Nishiyama1,2, Masahiro Nakatochi3, Atsushi Goto4, Motoki Iwasaki4, Tsuyoshi Hachiya5, Yoichi Sutoh5, Atsushi Shimizu5, Chaochen Wang1,2, Hideo Tanaka6, Miki Watanabe1, Akihiro Hosono1, Yuya Tamai1, Tamaki Yamada7, Taiki Yamaji4, Norie Sawada4, Kentaro Fukumoto8, Kotaro Otsuka8,9, Kozo Tanno9,10, Hiroaki Tomita11, Kaname Kojima12, Masao Nagasaki12, Atsushi Hozawa11, Asahi Hishida13, Tae Sasakabe13, Yuichiro Nishida14, Megumi Hara14, Hidemi Ito15, Isao Oze16, Yohko Nakamura17, Haruo Mikami17, Rie Ibusuki18, Toshiro Takezaki18, Teruhide Koyama19, Nagato Kuriyama19, Kaori Endoh20, Kiyonori Kuriki20, Tanvir C Turin21, Takashima Naoyuki21, Sakurako Katsuura-Kamano22, Hirokazu Uemura22, Rieko Okada13, Sayo Kawai13, Mariko Naito13,23, Yukihide Momozawa24, Michiaki Kubo24, Makoto Sasaki25,26, Masayuki Yamamoto12, Shoichiro Tsugane27, Kenji Wakai13, Sadao Suzuki1.
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 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 × 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 (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 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. © Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Entities:
Keywords: Mendelian randomization; alcohol consumption; genome-wide association study; usual sleep duration
Year: 2019 PMID： 30810208 DOI： 10.1093/sleep/zsz046
Source DB: PubMed Journal: Sleep ISSN： 0161-8105 Impact factor: 5.849