Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease.

Abstract

Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.

• Authors: Olivia M de Goede, Daniel C Nachun, Nicole M Ferraro, Michael J Gloudemans, Abhiram S Rao, Craig Smail, Tiffany Y Eulalio, François Aguet, Bernard Ng, Jishu Xu, Alvaro N Barbeira, Stephane E Castel, Sarah Kim-Hellmuth, YoSon Park, Alexandra J Scott, Benjamin J Strober, GTEx Consortium, Christopher D Brown, Xiaoquan Wen, Ira M Hall, Alexis Battle, Tuuli Lappalainen, Hae Kyung Im, Kristin G Ardlie, Sara Mostafavi, Thomas Quertermous, Karla Kirkegaard, Stephen B Montgomery
• Journal: Cell (Cell) Vol. 184 Issue 10 Pg. 2633-2648.e19 (05 13 2021) ISSN: 1097-4172 [Electronic] United States
• PMID: 33864768 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Long Noncoding

Topics

• Coronary Artery Disease (genetics)
• Diabetes Mellitus, Type 1 (genetics)
• Diabetes Mellitus, Type 2 (genetics)
• Disease (genetics)
• Gene Expression Profiling
• Genetic Variation
• Humans
• Inflammatory Bowel Diseases (genetics)
• Multifactorial Inheritance (genetics)
• Organ Specificity (genetics)
• Population (genetics)
• Quantitative Trait Loci
• RNA, Long Noncoding (genetics)
• Transcriptome