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Pietzner, M.* ; Wheeler, E.* ; Carrasco-Zanini, J.* ; Cortes, A.* ; Koprulu, M.* ; Wörheide, M. ; Oerton, E.* ; Cook, J.* ; Stewart, I.D.* ; Kerrison, N.D.* ; Luan, J.* ; Raffler, J. ; Arnold, M. ; Arlt, W.* ; O'Rahilly, S.* ; Kastenmüller, G. ; Gamazon, E.R.* ; Hingorani, A.D.* ; Scott, R.A.* ; Wareham, N.J.* ; Langenberg, C.*

Mapping the proteo-genomic convergence of human diseases.

Science 374:eabj1541 (2021)
Postprint DOI PMC
Open Access Green

Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3,892 plasma proteins to create a cis-anchored gene-protein-disease map of 1,859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to 1) connect etiologically related diseases, 2) provide biological context for new or emerging disorders, and 3) integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at GWAS loci, addressing a major barrier for experimental validation and clinical translation of genetic discoveries.

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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genetic Influences; Metaanalysis; Accumulation; Architecture; Association; Vitronectin; Atlas; Rspo1; Age
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 374, Issue: 6569, Pages: , Article Number: eabj1541 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Grants Gates Fellowship
UKRI/NIHR Strategic Priorities Award in Multimorbidity Research for the Multimorbidity Mechanism and Therapeutics Research Collaborative
NIH
NIH/NIA
National Institute on Aging
Wellcome Trust
Cambridge Trust
Medical Research Council