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

GTEx Consortium

doi:10.1016/j.cell.2021.03.050

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

GTEx Consortium

Cancer Prevention and Control (CPC)

Stanford University
Children's Mercy
Broad Institute
University of British Columbia
Rush University
University of Chicago
New York Genome Center
Columbia University
Ludwig Maximilian University of Munich
University of Pennsylvania
Washington University St. Louis
Johns Hopkins University
University of Michigan, Ann Arbor
Yale University
University of Washington

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

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.

Original language	English
Pages (from-to)	2633-2648.e19
Journal	Cell
Volume	184
Issue number	10
DOIs	https://doi.org/10.1016/j.cell.2021.03.050
State	Published - May 13 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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10.1016/j.cell.2021.03.050

Cite this

@article{88ad41216caf4d6db91fd7a6748c8f85,

title = "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.",

keywords = "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",

author = "\{GTEx Consortium\} and \{de Goede\}, \{Olivia M.\} and Nachun, \{Daniel C.\} and Ferraro, \{Nicole M.\} and Gloudemans, \{Michael J.\} and Rao, \{Abhiram S.\} and Craig Smail and Eulalio, \{Tiffany Y.\} and Fran{\c c}ois Aguet and Bernard Ng and Jishu Xu and Barbeira, \{Alvaro N.\} and Castel, \{Stephane E.\} and Sarah Kim-Hellmuth and Park, \{Yo Son\} and Scott, \{Alexandra J.\} and Strober, \{Benjamin J.\} and Shankara Anand and Stacey Gabriel and Getz, \{Gad A.\} and Aaron Graubert and Kane Hadley and Handsaker, \{Robert E.\} and Huang, \{Katherine H.\} and Xiao Li and MacArthur, \{Daniel G.\} and Meier, \{Samuel R.\} and Nedzel, \{Jared L.\} and Nguyen, \{Duyen T.\} and Segr{\`e}, \{Ayellet V.\} and Ellen Todres and Brunilda Balliu and Rodrigo Bonazzola and Andrew Brown and Conrad, \{Donald F.\} and Cotter, \{Daniel J.\} and Nancy Cox and Sayantan Das and Dermitzakis, \{Emmanouil T.\} and Jonah Einson and Engelhardt, \{Barbara E.\} and Eleazar Eskin and Flynn, \{Elise D.\} and Laure Fresard and Gamazon, \{Eric R.\} and Diego Garrido-Mart{\'i}n and Gay, \{Nicole R.\} and Roderic Guig{\'o} and Hamel, \{Andrew R.\} and Yuan He and Siminoff, \{Laura A.\}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = may,

day = "13",

doi = "10.1016/j.cell.2021.03.050",

language = "English",

volume = "184",

pages = "2633--2648.e19",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "10",

}

TY - JOUR

T1 - Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

AU - GTEx Consortium

AU - de Goede, Olivia M.

AU - Nachun, Daniel C.

AU - Ferraro, Nicole M.

AU - Gloudemans, Michael J.

AU - Rao, Abhiram S.

AU - Smail, Craig

AU - Eulalio, Tiffany Y.

AU - Aguet, François

AU - Ng, Bernard

AU - Xu, Jishu

AU - Barbeira, Alvaro N.

AU - Castel, Stephane E.

AU - Kim-Hellmuth, Sarah

AU - Park, Yo Son

AU - Scott, Alexandra J.

AU - Strober, Benjamin J.

AU - Anand, Shankara

AU - Gabriel, Stacey

AU - Getz, Gad A.

AU - Graubert, Aaron

AU - Hadley, Kane

AU - Handsaker, Robert E.

AU - Huang, Katherine H.

AU - Li, Xiao

AU - MacArthur, Daniel G.

AU - Meier, Samuel R.

AU - Nedzel, Jared L.

AU - Nguyen, Duyen T.

AU - Segrè, Ayellet V.

AU - Todres, Ellen

AU - Balliu, Brunilda

AU - Bonazzola, Rodrigo

AU - Brown, Andrew

AU - Conrad, Donald F.

AU - Cotter, Daniel J.

AU - Cox, Nancy

AU - Das, Sayantan

AU - Dermitzakis, Emmanouil T.

AU - Einson, Jonah

AU - Engelhardt, Barbara E.

AU - Eskin, Eleazar

AU - Flynn, Elise D.

AU - Fresard, Laure

AU - Gamazon, Eric R.

AU - Garrido-Martín, Diego

AU - Gay, Nicole R.

AU - Guigó, Roderic

AU - Hamel, Andrew R.

AU - He, Yuan

AU - Siminoff, Laura A.

PY - 2021/5/13

Y1 - 2021/5/13

N2 - 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.

AB - 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.

KW - Coronary Artery Disease/genetics

KW - Diabetes Mellitus, Type 1/genetics

KW - Diabetes Mellitus, Type 2/genetics

KW - Disease/genetics

KW - Gene Expression Profiling

KW - Genetic Variation

KW - Humans

KW - Inflammatory Bowel Diseases/genetics

KW - Multifactorial Inheritance/genetics

KW - Organ Specificity/genetics

KW - Population/genetics

KW - Quantitative Trait Loci

KW - RNA, Long Noncoding/genetics

KW - Transcriptome

UR - https://www.scopus.com/pages/publications/85105565888

U2 - 10.1016/j.cell.2021.03.050

DO - 10.1016/j.cell.2021.03.050

M3 - Article

C2 - 33864768

AN - SCOPUS:85105565888

SN - 0092-8674

VL - 184

SP - 2633-2648.e19

JO - Cell

JF - Cell

IS - 10

ER -

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

Abstract

UN SDGs

Keywords

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