• 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, and China pUlmonary Thromboembolism REgistry Study (CURES) investigators.
• 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, Beijing, 100029, China.
• Bmc Med. 2023 Apr 19; 21 (1): 153153.

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.© 2023. The Author(s).

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