Genomic evaluation of circulating proteins for drug target characterisation and precision medicine
Daniel Hvidberg Hansen,
Åsa K. Hedman,
Daria V. Zhernakova,
Sarah E Bergen,
Andrew D Bretherick,
Jesper R Gådin,
Jeremy D Gale,
Seung Hoan Choi,
John N. Danesh,
Federico de Masi,
Peter K Joshi,
Cecilia M. Lindgren,
Andrew P Morris,
Peter M Nilsson,
Jim F Wilson,
Adam S. Butterworth,
Michael V Holmes,
Posted 06 Apr 2020
bioRxiv DOI: 10.1101/2020.04.03.023804
Posted 06 Apr 2020
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. By mapping and replicating protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, we identified 467 pQTLs for 85 proteins. The pQTLs were used in combination with other sources of information to evaluate known drug targets, and suggest new target candidates or repositioning opportunities, underpinned by a) causality assessment using Mendelian randomization, b) pathway mapping using trans-pQTL gene assignments, and c) protein-centric polygenic risk scores enabling matching of plausible target mechanisms to sub-groups of individuals enabling precision medicine.
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