Cargando…
Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population
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 ass...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116678/ https://www.ncbi.nlm.nih.gov/pubmed/37076872 http://dx.doi.org/10.1186/s12916-023-02844-4 |
_version_ | 1785028477808803840 |
---|---|
author | Zhang, Zhu Li, Haobo Weng, Haoyi Zhou, Geyu Chen, Hong Yang, Guoru Zhang, Ping Zhang, Xiangyan Ji, Yingqun Ying, Kejing Liu, Bo Xu, Qixia Tang, Yongjun Zhu, Guangfa Liu, Zhihong Xia, Shuyue Yang, Xiaohong Dong, Lixia Zhu, Ling Zeng, Mian Yuan, Yadong Yang, Yuanhua Zhang, Nuofu Xu, Xiaomao Pang, Wenyi Zhang, Meng Zhang, Yu Zhen, Kaiyuan Wang, Dingyi Lei, Jieping Wu, Sinan Shu, Shi Zhang, Yunxia Zhang, Shuai Gao, Qian Huang, Qiang Deng, Chao Fu, Xi Chen, Gang Duan, Wenxin Wan, Jun Xie, Wanmu Zhang, Peng Wang, Shengfeng Yang, Peiran Zuo, Xianbo Zhai, Zhenguo Wang, Chen |
author_facet | Zhang, Zhu Li, Haobo Weng, Haoyi Zhou, Geyu Chen, Hong Yang, Guoru Zhang, Ping Zhang, Xiangyan Ji, Yingqun Ying, Kejing Liu, Bo Xu, Qixia Tang, Yongjun Zhu, Guangfa Liu, Zhihong Xia, Shuyue Yang, Xiaohong Dong, Lixia Zhu, Ling Zeng, Mian Yuan, Yadong Yang, Yuanhua Zhang, Nuofu Xu, Xiaomao Pang, Wenyi Zhang, Meng Zhang, Yu Zhen, Kaiyuan Wang, Dingyi Lei, Jieping Wu, Sinan Shu, Shi Zhang, Yunxia Zhang, Shuai Gao, Qian Huang, Qiang Deng, Chao Fu, Xi Chen, Gang Duan, Wenxin Wan, Jun Xie, Wanmu Zhang, Peng Wang, Shengfeng Yang, Peiran Zuo, Xianbo Zhai, Zhenguo Wang, Chen |
author_sort | Zhang, Zhu |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-02844-4. |
format | Online Article Text |
id | pubmed-10116678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101166782023-04-21 Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population Zhang, Zhu Li, Haobo Weng, Haoyi Zhou, Geyu Chen, Hong Yang, Guoru Zhang, Ping Zhang, Xiangyan Ji, Yingqun Ying, Kejing Liu, Bo Xu, Qixia Tang, Yongjun Zhu, Guangfa Liu, Zhihong Xia, Shuyue Yang, Xiaohong Dong, Lixia Zhu, Ling Zeng, Mian Yuan, Yadong Yang, Yuanhua Zhang, Nuofu Xu, Xiaomao Pang, Wenyi Zhang, Meng Zhang, Yu Zhen, Kaiyuan Wang, Dingyi Lei, Jieping Wu, Sinan Shu, Shi Zhang, Yunxia Zhang, Shuai Gao, Qian Huang, Qiang Deng, Chao Fu, Xi Chen, Gang Duan, Wenxin Wan, Jun Xie, Wanmu Zhang, Peng Wang, Shengfeng Yang, Peiran Zuo, Xianbo Zhai, Zhenguo Wang, Chen BMC Med Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-02844-4. BioMed Central 2023-04-19 /pmc/articles/PMC10116678/ /pubmed/37076872 http://dx.doi.org/10.1186/s12916-023-02844-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Zhang, Zhu Li, Haobo Weng, Haoyi Zhou, Geyu Chen, Hong Yang, Guoru Zhang, Ping Zhang, Xiangyan Ji, Yingqun Ying, Kejing Liu, Bo Xu, Qixia Tang, Yongjun Zhu, Guangfa Liu, Zhihong Xia, Shuyue Yang, Xiaohong Dong, Lixia Zhu, Ling Zeng, Mian Yuan, Yadong Yang, Yuanhua Zhang, Nuofu Xu, Xiaomao Pang, Wenyi Zhang, Meng Zhang, Yu Zhen, Kaiyuan Wang, Dingyi Lei, Jieping Wu, Sinan Shu, Shi Zhang, Yunxia Zhang, Shuai Gao, Qian Huang, Qiang Deng, Chao Fu, Xi Chen, Gang Duan, Wenxin Wan, Jun Xie, Wanmu Zhang, Peng Wang, Shengfeng Yang, Peiran Zuo, Xianbo Zhai, Zhenguo Wang, Chen Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title | Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title_full | Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title_fullStr | Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title_full_unstemmed | Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title_short | Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population |
title_sort | genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among han chinese population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116678/ https://www.ncbi.nlm.nih.gov/pubmed/37076872 http://dx.doi.org/10.1186/s12916-023-02844-4 |
work_keys_str_mv | AT zhangzhu genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT lihaobo genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wenghaoyi genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhougeyu genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT chenhong genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yangguoru genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangping genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangxiangyan genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT jiyingqun genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yingkejing genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT liubo genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT xuqixia genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT tangyongjun genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhuguangfa genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT liuzhihong genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT xiashuyue genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yangxiaohong genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT donglixia genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhuling genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zengmian genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yuanyadong genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yangyuanhua genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangnuofu genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT xuxiaomao genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT pangwenyi genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangmeng genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangyu genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhenkaiyuan genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wangdingyi genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT leijieping genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wusinan genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT shushi genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangyunxia genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangshuai genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT gaoqian genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT huangqiang genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT dengchao genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT fuxi genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT chengang genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT duanwenxin genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wanjun genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT xiewanmu genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhangpeng genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wangshengfeng genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT yangpeiran genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zuoxianbo genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT zhaizhenguo genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT wangchen genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation AT genomewideassociationanalysesidentifiednovelsusceptibilitylociforpulmonaryembolismamonghanchinesepopulation |