Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Folkersen, Lasse; Gustafsson, Stefan; Wang, Qin; Hansen, Daniel Hvidberg; Hedman, Åsa K.; Schork, Andrew J.; Page, Karen; Zhernakova, Daria V.; Wu, Yang; Peters, James E.; Eriksson, Niclas; Bergen, Sarah E.; Boutin, Thibaud; Bretherick, Andrew D.; Enroth, Stefan; Kalnapenkis, Anette; Gådin, Jesper R.; Suur, Bianca E; Chen, Yan; Matic, Ljubica; Gale, Jeremy D.; Lee, Julie; Zhang, Weidong; Quazi, Amira; Ala‐Korpela, Mika; Choi, Seung Hoan; Claringbould, Annique; Danesh, John; Smith, George Davey; Masi, Federico De; Elmståhl, Sölve; Engström, Gunnar; Fauman, Eric B.; Fernandez, Céline; Franke, Lude; Franks, Paul W.; Giedraitis, Vilmantas; Haley, Chris; Hamsten, Anders; Ingason, Andrés; Johansson, Åsa; Joshi, Peter K.; Lind, Lars; Lindgren, Cecilia M.; Lubitz, Steven A.; Palmer, Tom; Macdonald-Dunlop, Erin; Magnusson, Martin; Melander, Olle; Michaëlsson, Karl; Morris, Andrew P.; Mägi, Reedik; Nagle, Michael W.; Nilsson, Peter M.; Nilsson, Jan; Orho‐Melander, Marju; Polašek, Ozren; Prins, Bram P.; Pålsson, Erik; Qi, Ting; Sjögren, Marketa; Sundström, Johan; Surendran, Praveen; Võsa, Urmo; Werge, Thomas; Wernersson, Rasmus; Westra, Harm-Jan; Yang, Jian; Zhernakova, Alexandra; Ärnlöv, Johan; Fu, Jingyuan; Smith, J. G.; Esko, Tõnu; Hayward, Caroline; Gyllensten, Ulf; Landén, Mikael; Siegbahn, Agneta; Wilson, James F.; Wallentin, Lars; Butterworth, Adam S.; Holmes, Michael V.; Ingelsson, Erik; Mälarstig, Anders

doi:10.1038/s42255-020-00287-2

articleNature MetabolismOct 16, 2020HYBRID OA

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

LFLasse Folkersen SGStefan Gustafsson QWQin Wang DHDaniel Hvidberg Hansen ÅKÅsa K. Hedman

Karolinska Institutet · Uppsala University · +45 more institutions

PubMed

Indexed incrossrefdatacitepubmed

Abstract

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and…

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Topics

Keywords

Mendelian randomization
Computational biology
Biology
Biomarker
Human proteome project
Proteome
Disease
Biomarker discovery

UN Sustainable Development Goals

Peace, Justice and strong institutions

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