来源:Nature Communications 发布时间:2019/2/22 14:15:11
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影响早睡早起的基因变异|《自然-通讯》

论文标题:Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

期刊:Nature Communications

作者:Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. van Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron R. Jeffries, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth A. Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. Allebrandt, Jack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David A. Hinds, Richa Saxena, Michael N. Weedon,

发表时间:2019/01/29

数字识别码: 10.1038/s41467-018-08259-7

原文链接:http://t.cn/EVh4xdo

微信链接:https://mp.weixin.qq.com/s/2fbl93q4SOhsG2ZCofhVgQ

《自然-通讯》本周发表的一篇论文Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms指出,遗传变异会影响一个人是否是晨型人(morning person),并且会给心理健康带来潜在后果。这一大规模全基因组关联分析在之前研究的基础上进行了拓展,将与睡眠时型(在特定时间睡觉的先天倾向)可能相关的基因座总数从24个增加到351个。

图1:睡眠时型荟萃分析GWAS的曼哈顿图。 图源:Jones等

英国埃克塞特大学医学院的Michael Weedon及同事分析了两组人群(共697828人)的遗传变异,并寻找这些变异与自我报告的晨型程度之间的关系。在鉴定出的所有基因座中,有327个此前与睡眠时型并不相关。考虑到自我报告存在不准确或偏倚的情况,为了进一步验证这一发现,作者利用活动监测器对一部分参与者(共85760人)的睡眠情况进行了客观监测。结果证实,睡眠时型的基因座与入睡时间有关,但与睡眠质量和睡眠时间无关。作者使用多种统计方法研究了睡眠时型与疾病之间的关系,发现晨型人主观幸福感较强,同时抑郁症和精神分裂症风险较低。

图2:主观幸福感与睡眠时型暴露的孟德尔随机化散点图。图源:Jones等

作者指出大部分研究结果都基于自我报告(即问卷回答),可能会受到报告偏差的影响。因此,需要进一步研究才能确认这些遗传变异对患病风险是否具有因果作用。

摘要:Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

阅读论文全文请访问:http://t.cn/EVh4xdo

期刊介绍:Nature Communications (https://www.nature.com/ncomms/) is an open access journal that publishes high-quality research from all areas of the natural sciences. Papers published by the journal represent important advances of significance to specialists within each field.

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