Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-05512-x
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Funding
- National Institutes of Health [N01-HC-25195]
- Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD
- NIH [K23-HL116780]
- Massachusetts General Hospital Hassenfeld Research Scholar Award
- Helmholtz Zentrum Munchen - German Research Center for Environmental Health
- German Federal Ministry of Education and Research (BMBF)
- State of Bavaria
- Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ
- NHSBT [11-01-GEN]
- NIHR-BTRU in Donor Health and Genomics at the University of Cambridge [NIHR BTRU-2014-10024]
- NHSBT
- Merck and Co., Kenilworth, NJ, USA
- UK Medical Research Council [G0800270]
- British Heart Foundation [SP/09/002]
- UK National Institute for Health Research Cambridge Biomedical Research Centre
- European Research Council [268834]
- European Commission Framework Programme 7 [HEALTH-F2-2012-279233]
- Cambridge School of Clinical Medicine MRC/Sackler Prize PhD Studentship [MR/K50127X/1]
- Cambridge School of Clinical Medicine MB-PhD programme
- European Research Council (ERC) [268834] Funding Source: European Research Council (ERC)
- MRC [MR/L003120/1, G0800270] Funding Source: UKRI
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Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.
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