BMC Medicine (Apr 2023)
Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population
- Zhu Zhang,
- Haobo Li,
- Haoyi Weng,
- Geyu Zhou,
- Hong Chen,
- Guoru Yang,
- Ping Zhang,
- Xiangyan Zhang,
- Yingqun Ji,
- Kejing Ying,
- Bo Liu,
- Qixia Xu,
- Yongjun Tang,
- Guangfa Zhu,
- Zhihong Liu,
- Shuyue Xia,
- Xiaohong Yang,
- Lixia Dong,
- Ling Zhu,
- Mian Zeng,
- Yadong Yuan,
- Yuanhua Yang,
- Nuofu Zhang,
- Xiaomao Xu,
- Wenyi Pang,
- Meng Zhang,
- Yu Zhang,
- Kaiyuan Zhen,
- Dingyi Wang,
- Jieping Lei,
- Sinan Wu,
- Shi Shu,
- Yunxia Zhang,
- Shuai Zhang,
- Qian Gao,
- Qiang Huang,
- Chao Deng,
- Xi Fu,
- Gang Chen,
- Wenxin Duan,
- Jun Wan,
- Wanmu Xie,
- Peng Zhang,
- Shengfeng Wang,
- Peiran Yang,
- Xianbo Zuo,
- Zhenguo Zhai,
- Chen Wang,
- on behalf of the China pUlmonary Thromboembolism REgistry Study (CURES) investigators
Affiliations
- Zhu Zhang
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Haobo Li
- China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Haoyi Weng
- Shenzhen WeGene Clinical Laboratory; WeGene, Shenzhen Zaozhidao Technology Co. Ltd; Hunan Provincial Key Lab On Bioinformatics, School of Computer Science and Engineering, Central South University
- Geyu Zhou
- Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, College of Life Science and Biotechnology, Shanghai Jiao Tong University
- Hong Chen
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University
- Guoru Yang
- Department of Pulmonary and Critical Care Medicine, Weifang No.2 People’s Hospital
- Ping Zhang
- Department of Pulmonary and Critical Care Medicine, Dongguan People’s Hospital
- Xiangyan Zhang
- Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital
- Yingqun Ji
- Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital Affiliated by Tongji University
- Kejing Ying
- Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
- Bo Liu
- Department of Pulmonary and Critical Care Medicine, Department of Clinical Microbiology, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Linzi District People’s Hospital
- Qixia Xu
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China
- Yongjun Tang
- Department of Pulmonary and Critical Care Medicine, Xiangya Hospital Central South University
- Guangfa Zhu
- Department of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University
- Zhihong Liu
- Fuwai Hospital, Chinese Academy of Medical Science; National Center for Cardiovascular Diseases
- Shuyue Xia
- Department of Pulmonary and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College
- Xiaohong Yang
- Department of Pulmonary and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region
- Lixia Dong
- Department of Pulmonary and Critical Care Medicine, Tianjin Medical University General Hospital
- Ling Zhu
- Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital
- Mian Zeng
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University
- Yadong Yuan
- Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University
- Yuanhua Yang
- Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University
- Nuofu Zhang
- State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
- Xiaomao Xu
- Department of Pulmonary and Critical Care Medicine, Beijing Hospital
- Wenyi Pang
- Department of Pulmonary and Critical Care Medicine, Beijing Jishuitan Hospital
- Meng Zhang
- Department of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University
- Yu Zhang
- China-Japan Friendship Hospital, Capital Medical University; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Kaiyuan Zhen
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Dingyi Wang
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Jieping Lei
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Sinan Wu
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Shi Shu
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Yunxia Zhang
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Shuai Zhang
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Qian Gao
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Qiang Huang
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Chao Deng
- Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, College of Life Science and Biotechnology, Shanghai Jiao Tong University
- Xi Fu
- Shenzhen WeGene Clinical Laboratory; WeGene, Shenzhen Zaozhidao Technology Co. Ltd; Hunan Provincial Key Lab On Bioinformatics, School of Computer Science and Engineering, Central South University
- Gang Chen
- Shenzhen WeGene Clinical Laboratory; WeGene, Shenzhen Zaozhidao Technology Co. Ltd; Hunan Provincial Key Lab On Bioinformatics, School of Computer Science and Engineering, Central South University
- Wenxin Duan
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College
- Jun Wan
- Department of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University
- Wanmu Xie
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Peng Zhang
- Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
- Shengfeng Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University
- Peiran Yang
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College
- Xianbo Zuo
- Department of Dermatology, China-Japan Friendship Hospital, Beijing, China; Department of Pharmacy, China-Japan Friendship Hospital
- Zhenguo Zhai
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
- Chen Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
- on behalf of the China pUlmonary Thromboembolism REgistry Study (CURES) investigators
- DOI
- https://doi.org/10.1186/s12916-023-02844-4
- Journal volume & issue
-
Vol. 21,
no. 1
pp. 1 – 13
Abstract
Abstract Background A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. Methods We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. Results After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10−14), ABO rs582094 (p-value = 1.16 × 10−10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10−17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. Conclusions We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.
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