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 genetic study of circulating cardiovascular proteins in over 30,000 individuals identified 451 protein quantitative trait loci and mapped their regulatory pathways. The authors used Mendelian randomization to establish causal relationships between protein levels and disease, identifying 11 proteins with causal disease involvement suitable for future drug development and 7 known drug targets with validated regulatory mechanisms. The findings provide a genomic resource for precision medicine approaches to cardiovascular health.

UK applicability

The study's resource is internationally applicable and may inform UK clinical practice and precision medicine initiatives, though it does not directly address diet, farming systems, or food-based interventions. UK researchers could use these protein targets for biomarker development in NHS populations.

Key measures

Protein quantitative trait loci (pQTL); trans-pQTL gene and regulatory designations; causal inference via Mendelian randomization; validation through mouse knockdown experiments and clinical trial data

Outcomes reported

The study mapped protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, identifying 451 pQTLs for 85 proteins. Results were used to identify 11 proteins with causal evidence of disease involvement not previously targeted therapeutically and to evaluate existing drug targets.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Observational cohort with Mendelian randomization
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s42255-020-00287-2
Catalogue ID
BFmowc2by2-ls5fc8

Topic tags

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