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

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Bibtex

@article{9a451a80186c48e3984dad6861a35aa6,
title = "Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals",
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 suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.",
author = "Lasse Folkersen and Stefan Gustafsson and Qin Wang and Hansen, {Daniel Hvidberg} and Hedman, {{\AA}sa K} and Andrew Schork and Karen Page and Zhernakova, {Daria V} and Yang Wu and James Peters and Niclas Eriksson and Bergen, {Sarah E} and Boutin, {Thibaud S} and Bretherick, {Andrew D} and Stefan Enroth and Anette Kalnapenkis and G{\aa}din, {Jesper R} and Suur, {Bianca E} and Yan Chen and Ljubica Matic and Gale, {Jeremy D} and Julie Lee and Weidong Zhang and Amira Quazi and Mika Ala-Korpela and Choi, {Seung Hoan} and Annique Claringbould and John Danesh and {Davey Smith}, George and {de Masi}, Federico and S{\"o}lve Elmst{\aa}hl and Gunnar Engstr{\"o}m and Eric Fauman and Celine Fernandez and Lude Franke and Franks, {Paul W} and Vilmantas Giedraitis and Chris Haley and Anders Hamsten and Andres Ingason and {\AA}sa Johansson and Lindgren, {Cecilia M} and Martin Magnusson and Olle Melander and Nilsson, {Peter M} and Jan Nilsson and Marju Orho-Melander and Marketa Sj{\"o}gren and Jian Yang and Lars Wallentin and {SCALLOP Consortium}",
note = "These authors contributed equally: Lasse Folkersen, Stefan Gustafsson, Qin Wang, Michael V. Holmes, Erik Ingelsson, Anders M{\"a}larstig",
year = "2020",
month = oct,
doi = "10.1038/s42255-020-00287-2",
language = "English",
volume = "2",
pages = "1135--1148",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Nature",
number = "10",

}