Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases
Scott C Ritchie,
Samuel A Lambert,
Shu Mei Teo,
Mark D. Chaffin,
Willem H Ouwehand,
David J. Roberts,
Nicholas A Watkins,
Emanuele Di Angelantonio,
Brian G Drew,
Anna C. Calkin,
Amit V Khera,
Adam S. Butterworth,
Posted 19 Dec 2019
bioRxiv DOI: 10.1101/2019.12.14.876474
Posted 19 Dec 2019
Polygenic risk scores (PRSs) capture the genetic architecture of common diseases by aggregating genome-wide genetic variation into a single score that reflects an individual’s disease risk. These present new opportunities to identify molecular pathways involved in disease pathogenesis. We performed association analysis between PRSs and 3,442 plasma proteins in 3,175 healthy individuals, identifying 48 proteins whose levels associated with PRSs for coronary artery disease, chronic kidney disease, or type 2 diabetes. Integrative analyses of human and mouse data to characterise these associations revealed a role for polygenic effects on several well-known causal disease proteins and identified promising novel targets for future follow-up. We found implicated PRS-associated genes were responsive to dietary intervention in mice and showed strong evidence of druggability in humans, consistent with PRS-associated proteins having therapeutic potential. Overall, our study provides a framework for polygenic association studies, demonstrating the power of PRSs to unravel novel disease biology.
- Downloaded 1,588 times
- Download rankings, all-time:
- Site-wide: 9,903
- In genetics: 497
- Year to date:
- Site-wide: 7,343
- Since beginning of last month:
- Site-wide: 4,111
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!