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

TitlePopulation-scale tissue transcriptomics maps long non-coding RNAs to complex disease.
Publication TypeJournal Article
Year of Publication2021
Authorsde Goede, OM, Nachun, DC, Ferraro, NM, Gloudemans, MJ, Rao, AS, Smail, C, Eulalio, TY, Aguet, F, Ng, B, Xu, J, Barbeira, AN, Castel, SE, Kim-Hellmuth, S, Park, YS, Scott, AJ, Strober, BJ, Brown, CD, Wen, X, Hall, IM, Battle, A, Lappalainen, T, Im, HKyung, Ardlie, KG, Mostafavi, S, Quertermous, T, Kirkegaard, K, Montgomery, SB
Corporate AuthorsGTEx Consortium
JournalCell
Volume184
Issue10
Pagination2633-2648.e19
Date Published2021 05 13
ISSN1097-4172
KeywordsCoronary Artery Disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Disease, Gene Expression Profiling, Genetic Variation, Humans, Inflammatory Bowel Diseases, Multifactorial Inheritance, Organ Specificity, Population, Quantitative Trait Loci, RNA, Long Noncoding, Transcriptome
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.

DOI10.1016/j.cell.2021.03.050
Alternate JournalCell
PubMed ID33864768
PubMed Central IDPMC8651477
Grant ListR01 HL109512 / HL / NHLBI NIH HHS / United States
U01 HG009431 / HG / NHGRI NIH HHS / United States
R01 HG008150 / HG / NHGRI NIH HHS / United States
R01 MH107666 / MH / NIMH NIH HHS / United States
T32 NS105604 / NS / NINDS NIH HHS / United States
R01 MH109905 / MH / NIMH NIH HHS / United States
R01 MH106842 / MH / NIMH NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States
R01 GM124486 / GM / NIGMS NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 HL134817 / HL / NHLBI NIH HHS / United States
R01 MH125244 / MH / NIMH NIH HHS / United States
R01 HL135313 / HL / NHLBI NIH HHS / United States
R01 HL139478 / HL / NHLBI NIH HHS / United States
R01 HL142015 / HL / NHLBI NIH HHS / United States
K99 HG009916 / HG / NHGRI NIH HHS / United States
T15 LM007033 / LM / NLM NIH HHS / United States
R33 HL120757 / HL / NHLBI NIH HHS / United States
R01 HL142028 / HL / NHLBI NIH HHS / United States
R01 HG010067 / HG / NHGRI NIH HHS / United States
R01 AG066490 / AG / NIA NIH HHS / United States
R01 GM122924 / GM / NIGMS NIH HHS / United States
U41 HG009494 / HG / NHGRI NIH HHS / United States
R01 MH101822 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States