Integrative omics approach to identify the molecular architecture of inflammatory protein levels in healthy older adults
Robert F. Hillary,
Daniel L. McCartney,
Sarah E. Harris,
Sven Erik Ojavee,
David C Liewald,
Craig W Ritchie,
Kathryn L Evans,
Elliot M Tucker-Drob,
Naomi R. Wray,
Allan F. McRae,
Peter M. Visscher,
Ian J. Deary,
Matthew R. Robinson,
Riccardo E. Marioni
Posted 19 Feb 2020
bioRxiv DOI: 10.1101/2020.02.17.952135
Posted 19 Feb 2020
The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets. Therefore, in this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified three CpG sites spread across three proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to one polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease, and between IL12B and Crohn′s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
- Downloaded 351 times
- Download rankings, all-time:
- Site-wide: 43,574 out of 84,908
- In genomics: 3,872 out of 5,475
- Year to date:
- Site-wide: 4,996 out of 84,908
- Since beginning of last month:
- Site-wide: 12,185 out of 84,908
Downloads over time
Distribution of downloads per paper, site-wide
- 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!