基于自我报告的日间嗜睡的全基因组关联分析确定了 42 个位点，提示存在生物学亚型。
Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes.
机构信息
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
出版信息
Nat Commun. 2019 Aug 13;10(1):3503. doi: 10.1038/s41467-019-11456-7.
Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.
日间嗜睡（EDS）影响 10-20%的人群，并与大量的功能缺陷有关。在这里，我们在 UK Biobank 的 452071 名个体的 GWAS 中鉴定出 42 个与自我报告的日间嗜睡相关的位点，这些位点富集了在脑组织和神经元传递途径中表达的基因。我们在独立的斯堪的纳维亚队列中确认了 42 个 SNP 遗传风险评分对日间嗜睡的综合影响，以及对其他睡眠障碍（不宁腿综合征、失眠）和睡眠特征（持续时间、睡眠类型、加速度计衍生的睡眠效率和白天小睡或不活动）的影响。然而，个体日间嗜睡信号与客观的短睡眠和长睡眠以及睡眠连续性的标志物的关联存在差异。这 42 个嗜睡变体主要聚类成两种主要的综合生物学亚型——睡眠倾向和睡眠碎片化。与肥胖、冠心病、精神疾病、认知特征和生殖衰老也存在共享的遗传联系。
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