BACKGROUND The link between cardiometabolic disease and mental illness has been well established but remains incompletely explained. One hypothesis suggests that circadian rhythm dysregulation links cardiometabolic disease and mental illnesses. BMAL1 is a circadian rhythm regulatory gene. Human genetic studies have implicated BMAL1 in depression, schizophrenia, bipolar disorder as well as body mass index, blood pressure and lipid levels. OBJECTIVE We investigated the BMAL1 locus genetic variants for associations with both cardiometabolic and mental illness. METHODS Genetic and phenotypic data from UK Biobank (~500 000 participants) of White British, African-Caribbean, South Asian, white European and Multiple ancestries were used. Regression analyses using Plink 1.09 was used to identify significant associations, with Bonferroni multiple testing correction. Multiple ancestry meta-analyses using METAL software was used to investigate trans-ancestry consistency in genetic effects. FINDINGS We identified associations for body mass index, anhedonia, diastolic and systolic blood pressure, waist-hip ratio, major depressive disorder, neuroticism and risk-taking. Meta-analyses indicated that there are ancestry-wide and ancestry-specific effects on cardiometabolic, mental illness and related traits. CONCLUSIONS Our results suggest that the associations for mental illness (and related traits) and those for cardiometabolic traits are distinct rather than shared and that these associations were consistent across ancestry groups. CLINICAL IMPLICATIONS Further investigation into the tissue-specific roles of BMAL1 is required to fully understand the clinical impact of these findings.

中文翻译：

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昼夜节律调节基因 BMAL1 在精神病学、心理和心脏代谢性状中的遗传变异：一项跨血统英国生物样本库研究。


背景 心脏代谢疾病和精神疾病之间的联系已经得到充分证实，但仍未得到完全解释。一种假设表明，昼夜节律失调与心脏代谢疾病和精神疾病有关。BMAL1 是一个昼夜节律调节基因。人类遗传学研究表明，BMAL1 与抑郁症、精神分裂症、双相情感障碍以及体重指数、血压和血脂水平有关。目的 我们调查了 BMAL1 基因座遗传变异与心脏代谢和精神疾病的相关性。方法 使用来自英国生物样本库 （~500 000 名参与者） 的英国白人、非洲加勒比人、南亚人、欧洲白人和多血统的遗传和表型数据。使用 Plink 1.09 的回归分析用于识别显着关联，并采用 Bonferroni 多重检验校正。使用 METAL 软件的多血统荟萃分析用于研究遗传效应的跨血统一致性。结果： 我们确定了体重指数、快感缺乏、舒张压和收缩压、腰臀比、重度抑郁症、神经质和冒险的关联。荟萃分析表明，对心脏代谢、精神疾病和相关特征存在全血统和血统特异性的影响。结论 我们的结果表明，精神疾病（和相关特征）的关联和心脏代谢特征的关联是不同的，而不是共享的，并且这些关联在血统群体中是一致的。临床意义 需要进一步研究 BMAL1 的组织特异性作用，以充分了解这些发现的临床影响。