Phenome-wide screening for traits causally associated with the risk of coronary artery disease.,Journal of Human Genetics

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Phenome-wide screening for traits causally associated with the risk of coronary artery disease.
Journal of Human Genetics ( IF 2.6 ) Pub Date : 2020-01-07 , DOI: 10.1038/s10038-019-0716-z
Majid Nikpay ₁ , Sara Mohammadzadeh ₂

Affiliation

Using two independent approaches, Mendelian randomization and Polygenic risk score in a sample of 6194 CAD cases and 4287 controls of European ancestry, we did a comprehensive phenome-wide search (PheWAS) for traits that causally associated with the risk of CAD. We found 46 risk factors that represented diverse categories including cardiovascular, CNS (central nervous system), diabetes, lipids, immune, anthropometry, and life style features; moreover, we noted numerous evidences of genetic correlations and causal associations between risk factors from different categories. Among the identified risk factors, CAD showed highest genetic relatedness with thrombotic conditions. The most represented category was life style features (29%) with evidence of strong genetic overlap with CNS traits. Genetic variants associated with higher cognition were associated with life style characteristics and cardiometabolic features that lower the risk of CAD. Conditional analysis indicated this trend is in part attributed to higher age of first sexual intercourse (AFS) in those with higher cognition. Lower AFS was concordantly associated with higher risk of CAD in males, females, and the combined sample; furthermore, lower AFS was causally associated with several CAD-risk factors including, higher fasting insulin, fasting glucose, LDL, immature reticulocyte fraction, HbA1c levels, as well as, higher risk of T2D and pulmonary embolism but lower levels of HDL. These results indicate CAD is the outcome of several phenotypically distinct but genetically interrelated sources; moreover, we identified lower AFS as an independent causal risk factor of CAD and revealed its role in mediating the effect of other risk factors.

中文翻译：

全基因组筛查与冠心病风险相关的特征。

在6194例CAD病例和4287例欧洲血统对照的样本中，使用孟德尔随机化和多基因风险评分这两种独立的方法，我们对因果关系与CAD风险相关的特征进行了全面的全基因组搜索（PheWAS）。我们发现了46种危险因素，这些危险因素代表了各种类别，包括心血管，中枢神经系统（中枢神经系统），糖尿病，脂质，免疫，人体测量学和生活方式特征。此外，我们注意到许多证据表明不同类别的危险因素之间存在遗传相关性和因果关系。在确定的危险因素中，CAD显示与血栓形成状况的遗传相关性最高。最具代表性的类别是生活方式特征（29％），与中枢神经系统性状有很强的遗传重叠。与较高认知相关的遗传变异与生活方式特征和心脏代谢特征相关，从而降低了CAD的风险。条件分析表明，这种趋势部分归因于认知程度较高的人的首次性交年龄（AFS）。男性，女性和合并样本中较低的AFS与较高的CAD风险相关。此外，较低的AFS与多种CAD风险因素有因果关系，包括较高的空腹胰岛素，空腹血糖，LDL，网织红细胞成熟度，HbA1c水平，以及较高的T2D和肺栓塞风险，但HDL水平较低。这些结果表明，CAD是几种表型不同但遗传相关的来源的结果。此外，

更新日期：2020-01-07

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