Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population

BMC Medicine

卷:21

Research Article

Peng Zhang¹  Yu Zhang²  Haobo Li³  Chao Deng⁴  Geyu Zhou⁴  Xianbo Zuo⁵  Shengfeng Wang⁶  Mian Zeng⁷  Yuanhua Yang⁸  Xiaomao Xu⁹  Wenyi Pang¹⁰  Chen Wang¹¹  Shuyue Xia¹²  Shi Shu¹³  Yunxia Zhang¹³  Qiang Huang¹³  Qian Gao¹³  Zhenguo Zhai¹³  Wanmu Xie¹³  Zhu Zhang¹³  Shuai Zhang¹³  Bo Liu¹⁴  Ping Zhang¹⁵  Xiangyan Zhang¹⁶  Xiaohong Yang¹⁷  Ling Zhu¹⁸  Yingqun Ji¹⁹  Yadong Yuan²⁰  Lixia Dong²¹  Guoru Yang²²  Yongjun Tang²³  Hong Chen²⁴  Qixia Xu²⁵  Guangfa Zhu²⁶  Jun Wan²⁶  Meng Zhang²⁶  Kejing Ying²⁷  Zhihong Liu²⁸  Wenxin Duan²⁹  Peiran Yang²⁹  Kaiyuan Zhen³⁰  Dingyi Wang³¹  Jieping Lei³¹  Sinan Wu³¹  Xi Fu³²  Gang Chen³²  Haoyi Weng³²  Nuofu Zhang³³ 

[1] Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China;

[2] 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, 100029, Beijing, China;

[3] 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, 100029, Beijing, China;

[4] Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, College of Life Science and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China;

[5] Department of Dermatology, China-Japan Friendship Hospital, Beijing, China; Department of Pharmacy, China-Japan Friendship Hospital, No. 2, East Yinghua Road, Chaoyang District, 100029, Beijing, China;

[6] Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 100191, Beijing, China;

[7] Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, 510080, Guangzhou, China;

[8] Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 100026, Beijing, China;

[9] Department of Pulmonary and Critical Care Medicine, Beijing Hospital, 100080, Beijing, China;

[10] Department of Pulmonary and Critical Care Medicine, Beijing Jishuitan Hospital, 100035, Beijing, China;

[11] Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;National Center for Respiratory Medicine, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;National Clinical Research Center for Respiratory Diseases, Beijing, China;Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China;Department of Respiratory Medicine, Capital Medical University, Beijing, China;

[12] Department of Pulmonary and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, 110001, Shenyang, China;

[13] 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, 100029, Beijing, China;

[14] 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, 255400, Zibo, China;

[15] Department of Pulmonary and Critical Care Medicine, Dongguan People’s Hospital, 523059, Dongguan, China;

[16] Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, 550002, Guiyang, China;

[17] Department of Pulmonary and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001, Xinjiang, China;

[18] Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, 250021, Jinan, China;

[19] Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital Affiliated by Tongji University, 200120, Shanghai, China;

[20] Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, 050004, Shijiazhuang, China;

[21] Department of Pulmonary and Critical Care Medicine, Tianjin Medical University General Hospital, 300050, Tianjin, China;

[22] Department of Pulmonary and Critical Care Medicine, Weifang No.2 People’s Hospital, 261021, Weifang, China;

[23] Department of Pulmonary and Critical Care Medicine, Xiangya Hospital Central South University, 410008, Changsha, China;

[24] Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China;

[25] Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China, 230001, Hefei, China;

[26] Department of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University, 100029, Beijing, China;

[27] Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310020, Hangzhou, China;

[28] Fuwai Hospital, Chinese Academy of Medical Science; National Center for Cardiovascular Diseases, 100037, Beijing, China;

[29] Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, 100005, Beijing, China;

[30] 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, 100029, Beijing, China;

[31] 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, 100029, Beijing, China;

[32] 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, 518042, Shenzhen, China;

[33] 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, 510230, Guangzhou, China;

关键词: Pulmonary embolism;    GWAS;    Han Chinese;   

DOI  :  10.1186/s12916-023-02844-4

 received in 2022-10-04, accepted in 2023-03-22,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsWe 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.ResultsAfter 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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