Pulse Brain · Growing Health Evidence Index
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 identified protein quantitative trait loci for 90 cardiovascular proteins in over 30,000 individuals, generating 451 pQTLs across 85 proteins. The authors substantiated regulatory findings through mouse knockdown experiments and clinical trials, and used Mendelian randomization to identify 11 previously untargeted proteins with causal evidence of involvement in human disease. The work provides a genomic resource for precision studies of circulating proteins relevant to cardiovascular and metabolic health.

UK applicability

The findings are broadly applicable to UK biomedical research and may inform future clinical trial design and drug development strategies for cardiovascular disease. However, as a genomic mapping study in predominantly European ancestry populations, applicability to UK populations of non-European ancestry may require further investigation.

Key measures

Protein quantitative trait loci (pQTLs), trans-pQTL gene and regulatory designations, causal associations via Mendelian randomization

Outcomes reported

The study mapped protein quantitative trait loci (pQTLs) for 90 cardiovascular proteins across 30,931 individuals, identifying 451 pQTLs and 11 previously untargeted proteins with causal evidence of disease involvement. Findings were validated through mouse knockdown experiments and clinical trial evidence.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Observational cohort with functional validation and Mendelian randomization
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s42255-020-00287-2
Catalogue ID
BFmovi24gk-pabv92

Topic tags

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