Melroy-Greif Whitney E, Gizer Ian R, Wilhelmsen Kirk C, Ehlers Cindy L
Department of Neuroscience,The Scripps Research Institute,La Jolla,CA,USA.
Department of Psychological Sciences,University of Missouri,Columbia,MO,USA.
Twin Res Hum Genet. 2017 Dec;20(6):499-510. doi: 10.1017/thg.2017.62.
Diurnal preference (e.g., being an owl or lark) has been associated with several psychiatric disorders including bipolar disorder (BP), major depressive disorder, and substance use disorders. Previous large-scale genome-wide association studies (GWAS) aimed at identifying genetic influences on diurnal preference have exclusively included subjects of European ancestry. This study examined the genetic architecture of diurnal preference in two minority samples: a young adult sample of Mexican Americans (MAs), and a family-based sample of American Indians (AIs). Typed or imputed variants from exome chip data from the MA sample and low pass whole-genome sequencing from the AI cohort were analyzed using a mixed linear model approach for association with being an owl, as defined by a usual bedtime after 23:00 hrs. Genetic risk score (GRS) profiling detected shared genetic risk between evening preference and related disorders. Four variants in KIAA1549 like (KIAA1549L), a gene previously associated with attempted suicide in bipolar patients, were suggestively associated with being an owl at p < 1.82E-05; post hoc analyses showed the top variant trending in both the MA and AI cohorts at p = 2.50E-05 and p = .030, respectively. Variants associated with BP at p < .03 from the Psychiatric Genomics Consortium nominally predicted being an owl in the MA/AI cohort at p = .012. This study provides some additional evidence that genetic risk factors for BP also confer risk for being an owl in MAs/AIs and that evening preference may be a useful endophenotype for future studies of BP.
昼夜偏好（例如，是夜猫子还是早起的人）与包括双相情感障碍（BP）、重度抑郁症和物质使用障碍在内的几种精神疾病有关。以往旨在确定昼夜偏好的遗传影响的大规模全基因组关联研究（GWAS）只纳入了欧洲血统的受试者。本研究在两个少数族裔样本中研究了昼夜偏好的遗传结构：一个是墨西哥裔美国人（MAs）的年轻成人样本，另一个是美洲印第安人（AIs）的基于家庭的样本。使用混合线性模型方法分析了MA样本外显子芯片数据中的分型或推算变异以及AI队列的低通量全基因组测序数据，以确定与夜猫子型（定义为通常就寝时间在23:00之后）的关联性。遗传风险评分（GRS）分析检测到夜间偏好与相关疾病之间存在共同的遗传风险。KIAA1549样基因（KIAA1549L）中的四个变异，该基因先前与双相情感障碍患者的自杀未遂有关，在p < 1.82E-05时与夜猫子型有提示性关联；事后分析表明，在MA和AI队列中，顶级变异分别在p = 2.50E-05和p = 0.030时呈趋势性。来自精神病基因组学联盟的p < 0.03的与BP相关的变异在MA/AI队列中名义上预测夜猫子型的p值为0.012。本研究提供了一些额外的证据，表明BP的遗传风险因素也会使MAs/AIs成为夜猫子的风险增加，并且夜间偏好可能是未来BP研究中一个有用的内表型。
