Mapping the proteo-genomic convergence of human diseases

Maik Pietzner; Eleanor Wheeler; Julia Carrasco-Zanini; Adrian Cortes; Mine Koprulu; Maria Worheide; Erin Oerton; James Cook; Isobel Stewart; Nicola Kerrison; Jian'an Luan; Johannes Raffler; Matthias Arnold; Wiebke Arlt; Stephen O'Rahilly; Gabi Kastenmüller; Eric R Gamazon; Aroon D Hingorani; Robert Scott; Nicholas J  Wareham; Claudia Langenberg

doi:10.1126/science.abj1541

Mapping the proteo-genomic convergence of human diseases

Maik Pietzner, Eleanor Wheeler, Julia Carrasco-Zanini, Adrian Cortes, Mine Koprulu, Maria Worheide, Erin Oerton, James Cook, Isobel Stewart, Nicola Kerrison, Jian'an Luan, Johannes Raffler, Matthias Arnold, Wiebke Arlt, Stephen O'Rahilly, Gabi Kastenmüller, Eric R Gamazon, Aroon D Hingorani, Robert Scott, Nicholas J WarehamClaudia Langenberg

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	eabj1541
Journal	Science
Volume	374
Issue number	6569
Early online date	14 Oct 2021
DOIs	https://doi.org/10.1126/science.abj1541
Publication status	E-pub ahead of print - 14 Oct 2021

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This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 14/10/2021, DOI: 10.1126/science.abj1541
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Pietzner, M., Wheeler, E., Carrasco-Zanini, J., Cortes, A., Koprulu, M., Worheide, M., Oerton, E., Cook, J., Stewart, I., Kerrison, N., Luan, J., Raffler, J., Arnold, M., Arlt, W., O'Rahilly, S., Kastenmüller, G., Gamazon, E. R., Hingorani, A. D., Scott, R., ... Langenberg, C. (2021). Mapping the proteo-genomic convergence of human diseases. Science, 374(6569), Article eabj1541. Advance online publication. https://doi.org/10.1126/science.abj1541

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title = "Mapping the proteo-genomic convergence of human diseases",

abstract = "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.",

author = "Maik Pietzner and Eleanor Wheeler and Julia Carrasco-Zanini and Adrian Cortes and Mine Koprulu and Maria Worheide and Erin Oerton and James Cook and Isobel Stewart and Nicola Kerrison and Jian'an Luan and Johannes Raffler and Matthias Arnold and Wiebke Arlt and Stephen O'Rahilly and Gabi Kastenm{\"u}ller and Gamazon, {Eric R} and Hingorani, {Aroon D} and Robert Scott and Wareham, {Nicholas J} and Claudia Langenberg",

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Pietzner, M, Wheeler, E, Carrasco-Zanini, J, Cortes, A, Koprulu, M, Worheide, M, Oerton, E, Cook, J, Stewart, I, Kerrison, N, Luan, J, Raffler, J, Arnold, M, Arlt, W, O'Rahilly, S, Kastenmüller, G, Gamazon, ER, Hingorani, AD, Scott, R, Wareham, NJ & Langenberg, C 2021, 'Mapping the proteo-genomic convergence of human diseases', Science, vol. 374, no. 6569, eabj1541. https://doi.org/10.1126/science.abj1541

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AU - Oerton, Erin

AU - Cook, James

AU - Stewart, Isobel

AU - Kerrison, Nicola

AU - Luan, Jian'an

AU - Raffler, Johannes

AU - Arnold, Matthias

AU - Arlt, Wiebke

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AU - Kastenmüller, Gabi

AU - Gamazon, Eric R

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Mapping the proteo-genomic convergence of human diseases

Abstract

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