Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure-Reference-Cited by-同舟云学术

Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure

Published:2023-07-10 Issue:1 Volume:14 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Rasooly Danielle^ORCID,Peloso Gina M.^ORCID,Pereira Alexandre C.,Dashti Hesam,Giambartolomei Claudia^ORCID,Wheeler Eleanor^ORCID,Aung Nay^ORCID,Ferolito Brian R.,Pietzner Maik^ORCID,Farber-Eger Eric H.^ORCID,Wells Quinn Stanton,Kosik Nicole M.^ORCID,Gaziano Liam,Posner Daniel C.,Bento A. Patrícia,Hui Qin,Liu Chang^ORCID,Aragam Krishna^ORCID,Wang Zeyuan,Charest Brian,Huffman Jennifer E.^ORCID,Wilson Peter W. F.,Phillips Lawrence S.,Whittaker John^ORCID,Munroe Patricia B.^ORCID,Petersen Steffen E.^ORCID,Cho Kelly,Leach Andrew R.^ORCID,Magariños María Paula,Gaziano John Michael,Langenberg Claudia,Sun Yan V.^ORCID,Joseph Jacob,Casas Juan P.,

Abstract

AbstractWe conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-023-39253-3.pdf

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