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Tier 3 — Observational / field trialPeer-reviewed

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

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

Nature Metabolism · 2020

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Summary

This large-scale genomic study mapped the genetic regulation of 90 cardiovascular proteins in over 30,000 individuals, identifying 451 protein quantitative trait loci and substantiating findings through mouse knockdown experiments and clinical trial evidence. The authors evaluated existing drug targets and identified 11 novel proteins (including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12) with causal evidence of involvement in human disease that represent new therapeutic opportunities. These findings provide a comprehensive resource for precision medicine approaches to cardiovascular disease.

UK applicability

The findings are directly applicable to UK research and clinical practice, as cardiovascular disease is a leading cause of morbidity and mortality in the UK population. The identified drug targets and regulatory insights could inform future precision medicine strategies and drug development programmes within UK healthcare and pharmaceutical sectors.

Key measures

Protein quantitative trait loci (pQTL); trans-pQTL gene and regulatory designations; Mendelian randomisation estimates of causal protein–disease associations; mouse knockdown experiments; clinical trial data

Outcomes reported

The study mapped and replicated protein quantitative trait loci (pQTL) for 90 cardiovascular proteins across over 30,000 individuals, identifying 451 pQTLs for 85 proteins. It evaluated known drug targets and identified 11 novel proteins with causal evidence of involvement in human disease that had not previously been targeted.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Observational cohort with functional validation
Source type
Peer-reviewed study
Status
Published
Geography
Europe
System type
Human clinical
DOI
10.1038/s42255-020-00287-2
Catalogue ID
BFmou2mfu8-kps5hw

Topic tags

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