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Yao, C.* ; Chen, G.* ; Song, C.* ; Keefe, J.* ; Mendelson, M.* ; Huan, T.* ; Sun, B.B.* ; Laser, A. ; Maranville, J.C.* ; Wu, H.* ; Ho, J.E.* ; Courchesne, P.* ; Lyass, A.* ; Larson, M.G.* ; Gieger, C. ; Graumann, J.* ; Johnson, A.D.* ; Danesh, J.* ; Runz, H.* ; Hwang, S.-J.* ; Liu, C.* ; Butterworth, A.S.* ; Suhre, K.* ; Levy, D.*

Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.

Nat. Commun. 9:3268 (2018)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Coronary-artery-disease; Abo Blood-group; Heart-disease; Association; Variants; Expression; Atherosclerosis; Metaanalysis; Framingham; Risk

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 9, Issue: 1, Article Number: 3268

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)