Interactions between genetic variation and cellular environment in skeletal muscle gene expression
D. Leland Taylor,
David A. Knowles,
Laura J Scott,
Andrea H Ramirez,
Franceso Paolo Casale,
Brooke N. Wolford,
Ricardo Oliveira Albanus,
Stephen C.J. Parker,
Peter S. Chines,
Michael R Erdos,
Ryan P Welch,
Timo A. Lakka,
Heikki A Koistinen,
Francis S Collins
Posted 03 Feb 2017
bioRxiv DOI: 10.1101/105429 (published DOI: 10.1371/journal.pone.0195788)
Posted 03 Feb 2017
From whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discover cis acting genotype-environment interactions (GxE) - genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate interaction quantitative trait loci (iQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.
- Downloaded 597 times
- Download rankings, all-time:
- Site-wide: 48,007
- In genetics: 2,154
- Year to date:
- Site-wide: 133,020
- Since beginning of last month:
- Site-wide: 135,082
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!