Genetic determinants of daytime napping and effects on cardiometabolic health.
Genetic determinants of daytime napping and effects on cardiometabolic health.
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DOI：
10.1038/s41467-020-20585-3
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发表时间：
2021-02-10
影响因子：
16.6
通讯作者：
Saxena R
中科院分区：
文献类型：
--
作者：
Dashti HS;Daghlas I;Lane JM;Huang Y;Udler MS;Wang H;Ollila HM;Jones SE;Kim J;Wood AR;23andMe Research Team;Weedon MN;Aslibekyan S;Garaulet M;Saxena R
白天打盹是一种常见的、可遗传的行为，但其遗传基础和与心脏代谢健康的因果关系尚不清楚。在这里，我们在英国生物库(n = 452,633)中对自我报告的白天打盹进行了一项全基因组关联研究，并确定了123个基因座，其中61个在23andMe研究队列(n = 541,333)中重复。这些发现包括已建立的治疗睡眠障碍的药物靶点的错义变异(HCRTR1，HCRTR2)，与觉醒有关的基因(TRPC6，PNOC)，以及暗示肥胖-睡眠过多途径的基因(PNOC，PATJ)。关联信号与加速计测量的白天不活动持续时间一致，33个基因座与其他睡眠表型的基因座共定位。聚类分析确定了三个不同的促进NAP机制的簇，这些机制与心脏代谢结果具有不同的相关性。孟德尔随机化研究表明，更频繁的白天小睡与较高的血压和腰围之间存在潜在的因果联系。白天午睡的遗传基础以及白天午睡对心脏代谢健康的定向作用尚不清楚。在这里，作者在英国生物库和孟德尔随机化中对自我报告的白天小睡进行了一项全基因组范围的关联研究，以探索因果关系。
Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference. The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.