Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease
Yao Chen 1Larson Martin G. 2Levy Daniel 1Chen George 1Hwang Shih-Jen 1Song Ci 3Mendelson Michael 4Courchesne Paul 1Wu Hongsheng 5Liu Chunyu 1Suhre Karsten 6Gieger Christian 7Lyass Asya 8Johnson Andrew D. 1Huan Tianxiao 1Ho Jennifer E. 9Laser Annika 10Graumann Johannes11
作者信息
- 1. Framingham Heart Study||Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
- 2. Framingham Heart Study||Department of Biostatistics, Boston University School of Public Health
- 3. Framingham Heart Study||Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health||Department of Medical Sciences, Uppsala University||Department of Immunology, Genetics and Pathology, Uppsala University
- 4. Framingham Heart Study||Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health||Department of Cardiology
- 5. Computer Science and Networking, Wentworth Institute of Technology
- 6. Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar
- 7. Research Unit of Molecular Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Institute of Epidemiology II, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||German Center for Diabetes Research (DZD)
- 8. Framingham Heart Study||Department of Mathematics and Statistics, Boston University
- 9. Cardiovascular Research Center and Division of Cardiology, Department of Medicine
- 10. Research Unit of Molecular Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Institute of Epidemiology II, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health
- 11. Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute
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Abstract
Summary
Identifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.Key words
pQTL/GWAS/proteomics/cardiovascular disease/Mendelian randomization引用本文复制引用
Yao Chen,Larson Martin G.,Levy Daniel,Chen George,Hwang Shih-Jen,Song Ci,Mendelson Michael,Courchesne Paul,Wu Hongsheng,Liu Chunyu,Suhre Karsten,Gieger Christian,Lyass Asya,Johnson Andrew D.,Huan Tianxiao,Ho Jennifer E.,Laser Annika,Graumann Johannes.Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease[EB/OL].(2025-03-28)[2026-05-08].https://www.biorxiv.org/content/10.1101/136523.学科分类
医学研究方法/基础医学/遗传学
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