Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
Year: 2018
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nature Communications
Authors: Chen Yao, George Chen, Ci Song, Joshua Keefe, Michael Mendelson, Tianxiao Huan, Benjamin B. Sun, Annika Laser, Joseph C. Maranville, Hongsheng Wu, Jennifer E. Ho, Paul Courchesne, Asya Lyass, Martin G. Larson, Christian Gieger, Johannes Graumann, Andrew D. Johnson, John Danesh, Heiko Runz, Shih-Jen Hwang, Chunyu Liu, Adam S. Butterworth, Karsten Suhre, Daniel Levy
Institutions: National Institutes of Health, National Heart, Lung, and Blood Institute, Framingham Heart Study, Uppsala University, Boston Children's Hospital, University of Cambridge, Helmholtz Munich, Merck & Co., Inc., Rahway, NJ, USA (United States), Wentworth Institute of Technology, Massachusetts General Hospital, Boston University, German Center for Diabetes Research, Max Planck Institute for Heart and Lung Research, Wellcome Sanger Institute, British Heart Foundation, Addenbrooke's Hospital, Weill Cornell Medical College in Qatar, Weill Cornell Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Massachusetts General Hospital, Qatar Foundation, NHS Blood and Transplant, National Institute for Health and Care Research, British Heart Foundation, University of Cambridge, European Commission, Bundesministerium für Bildung und Forschung, National Institutes of Health, Weill Cornell Medical College, Weill Cornell Medicine - Qatar, Medical Research Council, Helmholtz Zentrum München, NIHR Cambridge Biomedical Research Centre, National Heart, Lung, and Blood Institute, FP7 Ideas: European Research Council, NHLBI Division of Intramural Research
Awards: G1177451333, G1359875377, G1490530680, NIHR Senior Investigator Award, NIHR Senior Investigator Award, Circulating Epigenetic Biomarkers for Personalized Cardiovascular Disease Prevention, G250621538, G2804450655, G3217060148, G3667269547, G385907487, The Role of Galectin-3 in Cardiac Remodeling and Heart Failure, G4194769985, G4211044638, G4584873075, G5164707915, G567453067, G587296758, The Framingham Heart Study, EPIC-CVD: Individualised CVD risk assessment: tailoring targeted and cost-effective approaches to Europe's diverse populations, Interplay of genetic, nutrient and lifestyle factors on incidence of coronary disease: EPIC-Heart, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), G8346449347, G9000124674
OpenAlex ID: W2886245587