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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Coronary-artery-disease; Abo Blood-group; Heart-disease; Association; Variants; Expression; Atherosclerosis; Metaanalysis; Framingham; Risk
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 3268 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-004
DOI 10.1038/s41467-018-05512-x
WOS ID WOS:000441608900008
Scopus ID 85051677773
PubMed ID 30111768
Erfassungsdatum 2018-09-14
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