Genetic overlap for ten cardiovascular diseases: A comprehensive gene-centric pleiotropic association analysis and Mendelian randomization study
Zeye Liu,
Jing Xu,
Jiangshan Tan,
Xiaofei Li,
Fengwen Zhang,
Wenbin Ouyang,
Shouzheng Wang,
Yuan Huang,
Shoujun Li,
Xiangbin Pan
Affiliations
Zeye Liu
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, Beijing 100037, China; Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Beijing 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Jing Xu
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China
Jiangshan Tan
Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
Xiaofei Li
Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Fengwen Zhang
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, Beijing 100037, China; Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Beijing 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Wenbin Ouyang
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, Beijing 100037, China; Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Beijing 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Shouzheng Wang
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, Beijing 100037, China; Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Beijing 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Yuan Huang
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Pediatric Cardiac Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China; Corresponding author
Shoujun Li
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Pediatric Cardiac Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China; Corresponding author
Xiangbin Pan
Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, Beijing 100037, China; Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Beijing 100037, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China; Corresponding author
Summary: Recent studies suggest that pleiotropic effects may explain the genetic architecture of cardiovascular diseases (CVDs). We conducted a comprehensive gene-centric pleiotropic association analysis for ten CVDs using genome-wide association study (GWAS) summary statistics to identify pleiotropic genes and pathways that may underlie multiple CVDs. We found shared genetic mechanisms underlying the pathophysiology of CVDs, with over two-thirds of the diseases exhibiting common genes and single-nucleotide polymorphisms (SNPs). Significant positive genetic correlations were observed in more than half of paired CVDs. Additionally, we investigated the pleiotropic genes shared between different CVDs, as well as their functional pathways and distribution in different tissues. Moreover, six hub genes, including ALDH2, XPO1, HSPA1L, ESR2, WDR12, and RAB1A, as well as 26 targeted potential drugs, were identified. Our study provides further evidence for the pleiotropic effects of genetic variants on CVDs and highlights the importance of considering pleiotropy in genetic association studies.
