Estimating the causal tissues for complex traits and diseases
Andrew A Brown,
Alexandra C Nica,
Emmanouil T. Dermitzakis
Posted 11 Sep 2016
bioRxiv DOI: 10.1101/074682 (published DOI: 10.1038/ng.3981)
Posted 11 Sep 2016
Interpretation of biological causes of the predisposing markers identified through Genome Wide Association Studies (GWAS) remains an open question. One direct and powerful way to assess the genetic causality behind GWAS is through expression quantitative trait loci (eQTLs). Here we describe a novel approach to estimate the tissues giving rise to the genetic causality behind a wide variety of GWAS traits, using the cis-eQTLs identified in 44 tissues of the GTEx consortium. We have adapted the Regulatory Trait Concordance (RTC) score, to on the one hand measure the tissue sharing probabilities of eQTLs, and also to calculate the probability that a GWAS and an eQTL variant tag the same underlying functional effect. We show that our tissue sharing estimates significantly correlate with commonly used estimates of tissue sharing. By normalizing the GWAS-eQTL probabilities with the tissue sharing estimates of the eQTLs, we can estimate the tissues from which GWAS genetic causality arises. Our approach not only indicates the gene mediating individual GWAS signals, but also can highlight tissues where the genetic causality for an individual trait is manifested.
- Downloaded 1,563 times
- Download rankings, all-time:
- Site-wide: 5,695 out of 92,411
- In genetics: 414 out of 4,738
- Year to date:
- Site-wide: 68,767 out of 92,411
- Since beginning of last month:
- Site-wide: 48,756 out of 92,411
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!