A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population
A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population
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DOI：
10.1038/s10038-022-01015-2
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发表时间：
2022-01-17
影响因子：
3.5
通讯作者：
Honda, Makoto
中科院分区：
文献类型：
--
作者：
Miyagawa, Taku;Shimada, Mihoko;Honda, Makoto
白天过度嗜睡的特征是持续感觉难以保持清醒，通常伴有不适当的睡眠发作。食欲素（hypocretin）是一种调节睡眠-觉醒周期和快速眼动睡眠的神经肽。在欧洲人群中进行的几项大规模全基因组关联研究（GWAS）发现了食欲素受体-1（OX 1 R）和-2（OX 2 R）的遗传变异，这些变异与睡眠特征（包括白天嗜睡）相关。为了确定与白天嗜睡相关的遗传变异，我们对来自东北医疗Megabank项目队列的14，329名日本人进行了前食欲素原、OX 1 R和OX 2 R遗传变异的关联研究。经Bonferroni校正后，OX 2 R的遗传变异与自我报告的日间嗜睡显著相关（rs 188018846：P = 8.4E-05）。此外，由欧洲GWAS鉴定的OX 2 R错义变异体在日本人群中显示与日间嗜睡名义上显著相关（p.Ile308Val，rs 2653349：P = 0.044）。OX 2 R的多种遗传变异可以影响一般人群的白天嗜睡。
Excessive daytime sleepiness is characterized by a persistent feeling of having trouble staying awake, typically with inappropriate sleep episodes. Orexin (hypocretin) is a neuropeptide that regulates sleep-wake cycles and rapid eye movement sleep. Several large-scale genome-wide association studies (GWASs) in European populations have found genetic variants in orexin receptor-1 (OX1R) and -2 (OX2R) that are associated with sleep traits including daytime sleepiness. To identify genetic variants associated with daytime sleepiness, we performed an association study of genetic variants in prepro-orexin, OX1R, and OX2R in 14,329 Japanese individuals from the Tohoku Medical Megabank Project cohort. A genetic variant in OX2R was significantly associated with self-reported daytime sleepiness after Bonferroni correction (rs188018846: P = 8.4E-05). In addition, a missense variant in OX2R identified by the European GWASs showed a nominally significant association with daytime sleepiness in a Japanese population (p.Ile308Val, rs2653349: P = 0.044). Multiple genetic variants in OX2R can affect daytime sleepiness in general populations.