Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations
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 ful...
| Main Authors: | , , , , , , , |
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BMC
2022-06-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-022-01067-1 |
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| author | Kai Wang Xian Shi Ziwei Zhu Xingjie Hao Liangkai Chen Shanshan Cheng Roger S. Y. Foo Chaolong Wang |
| author_facet | Kai Wang Xian Shi Ziwei Zhu Xingjie Hao Liangkai Chen Shanshan Cheng Roger S. Y. Foo Chaolong Wang |
| author_sort | Kai Wang |
| collection | DOAJ |
| description | 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 effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P < 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19, P = 3.26×10−5). Conclusions We confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD. |
| first_indexed | 2024-04-13T19:33:21Z |
| format | Article |
| id | doaj.art-7c25a5d179be46f9a5373766746689c9 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-13T19:33:21Z |
| publishDate | 2022-06-01 |
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| series | Genome Medicine |
| spelling | doaj.art-7c25a5d179be46f9a5373766746689c92022-12-22T02:33:07ZengBMCGenome Medicine1756-994X2022-06-0114111510.1186/s13073-022-01067-1Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populationsKai Wang0Xian Shi1Ziwei Zhu2Xingjie Hao3Liangkai Chen4Shanshan Cheng5Roger S. Y. Foo6Chaolong Wang7Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyCardiovascular Research Institute, Centre for Translational Medicine, National University Health SystemDepartment of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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 effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P < 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19, P = 3.26×10−5). Conclusions We confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD.https://doi.org/10.1186/s13073-022-01067-1Mendelian randomizationClinical factorsCoronary artery diseaseCausal inferenceRed blood cellsUric acid |
| spellingShingle | Kai Wang Xian Shi Ziwei Zhu Xingjie Hao Liangkai Chen Shanshan Cheng Roger S. Y. Foo Chaolong Wang Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations Genome Medicine Mendelian randomization Clinical factors Coronary artery disease Causal inference Red blood cells Uric acid |
| title | Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations |
| title_full | Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations |
| title_fullStr | Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations |
| title_full_unstemmed | Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations |
| title_short | Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations |
| title_sort | mendelian randomization analysis of 37 clinical factors and coronary artery disease in east asian and european populations |
| topic | Mendelian randomization Clinical factors Coronary artery disease Causal inference Red blood cells Uric acid |
| url | https://doi.org/10.1186/s13073-022-01067-1 |
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