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

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art_RASOOLY_Genomewide_association_analysis_and_Mendelian_randomization_proteomics_identify_2023.PDF (1.93 MB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PORTFOLIO
Autores
RASOOLY, Danielle
PELOSO, Gina M.
DASHTI, Hesam
GIAMBARTOLOMEI, Claudia
WHEELER, Eleanor
AUNG, Nay
FEROLITO, Brian R.
PIETZNER, Maik
FARBER-EGER, Eric H.
Citação
NATURE COMMUNICATIONS, v.14, n.1, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
We 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. Here, the authors perform a large-scale meta-analysis of genome-wide association studies and cis-MR proteomics to identify protein biomarkers and drug targets for heart failure.
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URI
https://observatorio.fm.usp.br/handle/OPI/56418
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - ODS/03