Centre for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TT, UK.
Genes (Basel). 2021 Jul 1;12(7):1029. doi: 10.3390/genes12071029.
Observational and experimental evidence has linked chronotype to both psychological and cardiometabolic traits. Recent Mendelian randomization (MR) studies have investigated direct links between chronotype and several of these traits, often in isolation of outside potential mediating or moderating traits. We mined the EpiGraphDB MR database for calculated chronotype-trait associations (-value < 5 × 10). We then re-analyzed those relevant to metabolic or mental health and investigated for statistical evidence of horizontal pleiotropy. Analyses passing multiple testing correction were then investigated for confounders, colliders, intermediates, and reverse intermediates using the EpiGraphDB database, creating multiple chronotype-trait interactions among each of the the traits studied. We revealed 10 significant chronotype-exposure associations (false discovery rate < 0.05) exposed to 111 potential previously known confounders, 52 intermediates, 18 reverse intermediates, and 31 colliders. Chronotype-lipid causal associations collided with treatment and diabetes effects; chronotype-bipolar associations were mediated by breast cancer; and chronotype-alcohol intake associations were impacted by confounders and intermediate variables including known zeitgebers and molecular traits. We have reported the influence of chronotype on several cardiometabolic and behavioural traits, and identified potential confounding variables not reported on in studies while discovering new associations to drugs and disease.
观察性和实验证据将时型与心理和心脏代谢特征联系起来。最近的孟德尔随机化（MR）研究调查了时型与其中一些特征之间的直接联系，通常是在不考虑外部潜在中介或调节特征的情况下进行的。我们从 EpiGraphDB MR 数据库中挖掘了计算出的时型-特征关联（p 值 < 5×10）。然后，我们重新分析了与代谢或心理健康相关的那些，并调查了水平多效性的统计证据。然后使用 EpiGraphDB 数据库调查通过多重测试校正的分析是否存在混杂因素、共发因素、中间因素和反向中间因素，在每个研究的特征之间创建多个时型-特征相互作用。我们揭示了 10 个显著的时型-暴露关联（假发现率 < 0.05），这些关联涉及 111 个潜在的先前已知混杂因素、52 个中间因素、18 个反向中间因素和 31 个共发因素。时型-脂质因果关联与治疗和糖尿病效应发生冲突；时型-双相情感障碍关联由乳腺癌介导；时型-饮酒摄入关联受到混杂因素和中间变量的影响，包括已知的生物钟和分子特征。我们已经报告了时型对几种心脏代谢和行为特征的影响，并确定了研究中未报告的潜在混杂变量，同时发现了与药物和疾病的新关联。
