Hu Youna, Shmygelska Alena, Tran David, Eriksson Nicholas, Tung Joyce Y, Hinds David A
23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
Department of Biological Sciences, San Jose State University, San Jose, California 95112 USA.
Nat Commun. 2016 Feb 2;7:10448. doi: 10.1038/ncomms10448.
Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.
昼夜节律是生物体几乎普遍具有的特征,影响着几乎所有的生物过程。我们对早晨或晚上的先天偏好由我们昼夜节律的阶段决定。我们对自我报告的晨型进行了全基因组关联分析,随后对生物途径和相关表型进行了分析。我们鉴定出15个显著相关的位点,包括7个靠近已确定的昼夜节律基因的位点(RGS16附近的rs12736689,P = 7.0×10^(-18);VIP附近的rs9479402,P = 3.9×10^(-11);PER2附近的rs55694368,P = 2.6×10^(-9);HCRTR2附近的rs35833281,P = 3.7×10^(-9);RASD1附近的rs11545787,P = 1.4×10^(-8);PER3附近的rs11121022,P = 2.0×10^(-8);FBXL3附近的rs9565309,P = 3.5×10^(-8))。昼夜节律和光转导途径在我们的结果中显著富集。晨型与失眠及其他睡眠表型相关;并且与体重指数和抑郁相关,但我们在孟德尔随机化分析中未发现因果关系的证据。我们的发现强化了当前对昼夜节律生物学的理解,并将为未来的研究提供指导。