Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations

作者：Kai You Wang, Xian Shi, Ziwei Zhu, Xingjie Hao, Liangkai Chen, Shanshan Cheng, Roger Foo, Chaolong Wang · 发表于：Genome Medicine · 年份：2022 · DOI：10.1186/s13073-022-01067-1 · 被引用次数：76 · 研究领域：Genetic Associations and Epidemiology、Kruppel-like factors research、Hemoglobinopathies and Related Disorders

Abstract Background Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations. Methods We collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis. Results Univariable MR analyses identified reliable causal evidence (P< 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effec...