Mapping the proteo-genomic convergence of human diseases.
Stewart, Isobel D
Kerrison, Nicola D
Scott, Robert A
Science (New York, N.Y.)
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Pietzner, M., Wheeler, E., Carrasco-Zanini, J., Cortes, A., Koprulu, M., Wörheide, M. A., Oerton, E., et al. (2021). Mapping the proteo-genomic convergence of human diseases.. Science (New York, N.Y.), eabj1541. https://doi.org/10.1126/science.abj1541
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.
The Fenland Study (10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1). We further acknowledge support for genomics from the Medical Research Council (MC_PC_13046). ERG is supported by the National Institutes of Health (NIH) Awards R35HG010718, R01HG011138, R01GM140287, and NIH/NIA AG068026. MAW, MA, and GK are supported by grants from the National Institute on Aging (NIA): U01 AG061359, RF1 AG057452, and RF1 AG059093). JCZ is supported by a 4-year Wellcome Trust PhD Studentship and the Cambridge Trust; MK is supported by a Gates Fellowship; CL, EW, MP, JL, EO, IS, NK, and NJW are funded by the Medical Research Council (MC_UU_00006/1 - Aetiology and Mechanisms). This work was supported in part by the UKRI/NIHR Strategic Priorities Award in Multimorbidity Research for the Multimorbidity Mechanism and Therapeutics Research Collaborative (MR/V033867/1).
External DOI: https://doi.org/10.1126/science.abj1541
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329133
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