Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity.
Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity.
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通过环境研究在日光和时型中花费的时间研究确定了光敏感性的基础。
作者：
光是同步人类生物钟的主要刺激。生物钟对光的敏感度存在很大的个体差异。目前对这些个体差异的遗传基础知之甚少。我们对来自英国生物银行队列的 280 897 名个体进行了全基因组基因与环境相互作用研究 (GWIS)，以确定调节白天光照射对生物钟（个人时间偏好）影响的遗传变异，作为日光对昼夜节律系统影响的“光敏感性”变异。我们发现了一个映射到 ARL14EP 基因的全基因组显着 SNP（rs3847634；p < 5 × 10−8），其中发现额外的次要等位基因可以增强日间光照的早晨效应（= −.03，SE = 0.005），并且与大脑和视网膜组织中基因 ARL14EP 表达增加相关。基因特性分析显示，G 蛋白偶联谷氨酸受体信号通路中的基因和 Per2+ 下丘脑神经元表达的基因的光敏感性位点富集。 Bonferroni 连锁不平衡评分回归发现，较高的光敏感度 GWIS 与较晚的睡眠时间型和较短的睡眠时间存在显着的遗传相关性。名义上，较高的光敏感度与失眠症状和创伤后应激障碍（PTSD）风险存在遗传相关性。这项研究首次评估了光在生物钟基因组学中的重要作用，也是揭示人类昼夜节律光敏感性的遗传结构及其与睡眠和心理健康的联系的关键的第一步。
Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences. We performed a genome-wide gene-by-environment interaction study (GWIS) in 280 897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as “light sensitivity” variants for the impact of daylight on the circadian system. We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p < 5 × 10−8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure ( = −.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and genes expressed in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified Bonferroni significant genetic correlations of greater light sensitivity GWIS with later chronotype and shorter sleep duration. Greater light sensitivity was nominally genetically correlated with insomnia symptoms and risk for post-traumatic stress disorder (PTSD). This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental health.
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5.8
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