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Genetic influences on evening preference overlap with those for bipolar disorder in a sample of Mexican Americans and American Indians

机译：在墨西哥裔美国人和美洲印第安人样本中对傍晚偏好的遗传影响与双相情感障碍的遗传影响重叠

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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=0.030, respectively. Variants associated with BP at p<0.03 from the Psychiatric Genomics Consortium nominally predicted being an owl in the MA/AI cohort at p=0.012. 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.
机译：昼夜偏好（例如“猫头鹰”或“百灵鸟”）与多种精神疾病有关，包括躁郁症，严重抑郁症和药物滥用症。以前旨在确定遗传因素对昼夜偏好的影响的大规模全基因组关联研究（GWAS）仅包括欧洲血统的对象。这项研究在两个少数族裔样本中研究了昼夜偏好的遗传结构：墨西哥裔美国人（MAs）的年轻成年人样本和美洲印第安人（AIs）的家庭样本。使用混合线性模型方法分析来自MA样本的外显子组芯片数据的分型或估算变异以及来自AI队列的低通全基因组测序，以与猫头鹰相关联，如23:00小时后的通常就寝时间所定义的。遗传风险评分（GRS）分析检测到晚上偏爱与相关疾病之间存在共同的遗传风险。 KIAA1549的四个变异体（KIAA1549L）是一种先前与双相情感障碍患者自杀未遂有关的基因，暗示其与猫头鹰在p <1.82E-05上相关。事后分析显示，MA和AI队列的最高变异趋势分别为p = 2.50E-05和p = 0.030。来自精神病学基因组学联盟的p <0.03时与BP相关的变体名义上预测是MA / AI队列中p = 0.012时的猫头鹰。这项研究提供了一些额外的证据，证明BP的遗传风险因素也赋予了MAs / AIs中猫头鹰的风险，并且夜间偏爱可能是BP未来研究的有用内表型。

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