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

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; Shankara Anand; Stacey Gabriel; Gad A Getz; Aaron Graubert; Kane Hadley; Robert E Handsaker; Katherine H Huang; Xiao Li; Daniel G MacArthur; Samuel R Meier; Jared L Nedzel; Duyen T Nguyen; Ayellet V Segrè; Ellen Todres; Brunilda Balliu; Rodrigo Bonazzola; Andrew Brown; Donald F Conrad; Daniel J Cotter; Nancy Cox; Sayantan Das; Emmanouil T Dermitzakis; Jonah Einson; Barbara E Engelhardt; Eleazar Eskin; Elise D Flynn; Laure Fresard; Eric R Gamazon; Diego Garrido-Martín; Nicole R Gay; Roderic Guigó; Andrew R Hamel; Yuan He; Paul J Hoffman; Farhad Hormozdiari; Lei Hou; Brian Jo; Silva Kasela; Seva Kashin; Manolis Kellis; Alan Kwong; Xin Li; Yanyu Liang; Serghei Mangul; Pejman Mohammadi; Manuel Muñoz-Aguirre; Andrew B Nobel; Meritxell Oliva; Yongjin Park; Princy Parsana; Ferran Reverter; John M Rouhana; Chiara Sabatti; Ashis Saha; Matthew Stephens; Barbara E Stranger; Nicole A Teran; Ana Viñuela; Gao Wang; Fred Wright; Valentin Wucher; Yuxin Zou; Pedro G Ferreira; Gen Li; Marta Melé; Esti Yeger-Lotem; Debra Bradbury; Tanya Krubit; Jeffrey A McLean; Liqun Qi; Karna Robinson; Nancy V Roche; Anna M Smith; David E Tabor; Anita Undale; Jason Bridge; Lori E Brigham; Barbara A Foster; Bryan M Gillard; Richard Hasz; Marcus Hunter; Christopher Johns; Mark Johnson; Ellen Karasik; Gene Kopen; William F Leinweber; Alisa McDonald; Michael T Moser; Kevin Myer; Kimberley D Ramsey; Brian Roe; Saboor Shad; Jeffrey A Thomas; Gary Walters; Michael Washington; Joseph Wheeler; Scott D Jewell; Daniel C Rohrer; Dana R Valley; David A Davis; Deborah C Mash; Mary E Barcus; Philip A Branton; Leslie Sobin; Laura K Barker; Heather M Gardiner; Maghboeba Mosavel; Laura A Siminoff; Paul Flicek; Maximilian Haeussler; Thomas Juettemann; W. James Kent; Christopher M Lee; Conner C Powell; Kate R Rosenbloom; Magali Ruffier; Dan Sheppard; Kieron Taylor; Stephen J Trevanion; Daniel R Zerbino; Nathan S Abell; Joshua Akey; Lin Chen; Kathryn Demanelis; Jennifer A Doherty; Andrew P Feinberg; Kasper D Hansen; Peter F Hickey; Farzana Jasmine; Lihua Jiang; Rajinder Kaul; Muhammad G Kibriya; Jin Billy Li; Qin Li; Shin Lin; Sandra E Linder; Brandon L Pierce; Lindsay F Rizzardi; Andrew D Skol; Kevin S Smith; Michael Snyder; John Stamatoyannopoulos; Hua Tang; Meng Wang; Latarsha J Carithers; Ping Guan; Susan E Koester; A. Roger Little; Helen M Moore; Concepcion R Nierras; Abhi K Rao; Jimmie B Vaught; Simona Volpi; 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; GTEx Consortium

doi:10.1016/j.cell.2021.03.050

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

Journal article

Peer reviewed

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

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, …

Cell, Vol.184(10), pp.2633-2648.e19

2021-05-13

DOI: https://doi.org/10.1016/j.cell.2021.03.050

PMID: 33864768

Abstract

expression quantitative trait loci

GTEx

lncRNA

complex trait

co-expression

long non-coding RNA

eQTL

colocalization

Disease

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. [Display omitted] •29% of lncRNA genes with eQTLs show tissue-specific genetic regulation•Co-expression networks and single-cell data provide annotations for 94% of lncRNAs•Rare variants near lncRNA expression outliers impact complex traits, like BMI•We identify 800 lncRNA-trait relationships not explained by protein-coding genes A systematic analysis of NIH Genotype Tissue Expression (GTEx) project data provides insights into lncRNA expression patterns and functions, explores the impact of genetic variation on lncRNAs, and connects lncRNAs to complex traits and human disease.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.196 Micro & Long Noncoding RNA; 1.196.921 lncRNA
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Details

Title: Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease
Creators: Olivia M de Goede - Department of Genetics, Stanford University, Stanford, CA 94305, USA
Daniel C Nachun - Department of Pathology, Stanford University, Stanford, CA 94305, USA
Nicole M Ferraro - Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA
Michael J Gloudemans - Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA
Abhiram S Rao - Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
Craig Smail - Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA
Tiffany Y Eulalio - Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA
François Aguet - The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Bernard Ng - Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Jishu Xu - Rush Alzheimer’s Disease Center, Rush University, Chicago, Illinois 60612, USA
Alvaro N Barbeira - Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Stephane E Castel - New York Genome Center, New York, NY 10013, USA
Sarah Kim-Hellmuth - New York Genome Center, New York, NY 10013, USA
YoSon Park - Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Alexandra J Scott - McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
Benjamin J Strober - Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Shankara Anand
Stacey Gabriel
Gad A Getz
Aaron Graubert
Kane Hadley
Robert E Handsaker
Katherine H Huang
Xiao Li
Daniel G MacArthur
Samuel R Meier
Jared L Nedzel
Duyen T Nguyen
Ayellet V Segrè
Ellen Todres
Brunilda Balliu
Rodrigo Bonazzola
Andrew Brown
Donald F Conrad
Daniel J Cotter
Nancy Cox
Sayantan Das
Emmanouil T Dermitzakis
Jonah Einson
Barbara E Engelhardt
Eleazar Eskin
Elise D Flynn
Laure Fresard
Eric R Gamazon
Diego Garrido-Martín
Nicole R Gay
Roderic Guigó
Andrew R Hamel
Yuan He
Paul J Hoffman
Farhad Hormozdiari
Lei Hou
Brian Jo
Silva Kasela
Seva Kashin
Manolis Kellis
Alan Kwong
Xin Li
Yanyu Liang
Serghei Mangul
Pejman Mohammadi
Manuel Muñoz-Aguirre
Andrew B Nobel
Meritxell Oliva
Yongjin Park
Princy Parsana
Ferran Reverter
John M Rouhana
Chiara Sabatti
Ashis Saha
Matthew Stephens
Barbara E Stranger
Nicole A Teran
Ana Viñuela
Gao Wang
Fred Wright
Valentin Wucher
Yuxin Zou
Pedro G Ferreira
Gen Li
Marta Melé
Esti Yeger-Lotem
Debra Bradbury
Tanya Krubit
Jeffrey A McLean
Liqun Qi
Karna Robinson
Nancy V Roche
Anna M Smith
David E Tabor
Anita Undale
Jason Bridge
Lori E Brigham
Barbara A Foster
Bryan M Gillard
Richard Hasz
Marcus Hunter
Christopher Johns
Mark Johnson
Ellen Karasik
Gene Kopen
William F Leinweber
Alisa McDonald
Michael T Moser
Kevin Myer
Kimberley D Ramsey
Brian Roe
Saboor Shad
Jeffrey A Thomas
Gary Walters
Michael Washington
Joseph Wheeler
Scott D Jewell
Daniel C Rohrer
Dana R Valley
David A Davis
Deborah C Mash
Mary E Barcus
Philip A Branton
Leslie Sobin
Laura K Barker
Heather M Gardiner
Maghboeba Mosavel
Laura A Siminoff
Paul Flicek
Maximilian Haeussler
Thomas Juettemann
W. James Kent
Christopher M Lee
Conner C Powell
Kate R Rosenbloom
Magali Ruffier
Dan Sheppard
Kieron Taylor
Stephen J Trevanion
Daniel R Zerbino
Nathan S Abell
Joshua Akey
Lin Chen
Kathryn Demanelis
Jennifer A Doherty
Andrew P Feinberg
Kasper D Hansen
Peter F Hickey
Farzana Jasmine
Lihua Jiang
Rajinder Kaul
Muhammad G Kibriya
Jin Billy Li
Qin Li
Shin Lin
Sandra E Linder
Brandon L Pierce
Lindsay F Rizzardi
Andrew D Skol
Kevin S Smith
Michael Snyder
John Stamatoyannopoulos
Hua Tang
Meng Wang
Latarsha J Carithers
Ping Guan
Susan E Koester
A. Roger Little
Helen M Moore
Concepcion R Nierras
Abhi K Rao
Jimmie B Vaught
Simona Volpi
Christopher D Brown - Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Xiaoquan Wen - Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
Ira M Hall - Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
Alexis Battle - Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Tuuli Lappalainen - New York Genome Center, New York, NY 10013, USA
Hae Kyung Im - Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Kristin G Ardlie - The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Sara Mostafavi - Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA
Thomas Quertermous - Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA
Karla Kirkegaard - Department of Genetics, Stanford University, Stanford, CA 94305, USA
Stephen B Montgomery - Department of Genetics, Stanford University, Stanford, CA 94305, USA
GTEx Consortium
Publication Details: Cell, Vol.184(10), pp.2633-2648.e19
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; UMMG Department of Neurology
Language: English
Resource Type: Journal article
PMID: 33864768
Record Identifier: 991031598719002976