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

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
GTEx co-expression colocalization complex trait disease eQTL expression quantitative trait loci lncRNA long non-coding RNA

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
13 05 2021
Historique:
received: 10 12 2019
revised: 16 10 2020
accepted: 24 03 2021
pubmed: 18 4 2021
medline: 22 12 2021
entrez: 17 4 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2021.03.050 PMID: 33864768 PMC: PMC8651477
pubmed: 33864768
pii: S0092-8674(21)00381-0
doi: 10.1016/j.cell.2021.03.050
pmc: PMC8651477
mid: NIHMS1688845
pii:
doi:

Substances chimiques

RNA, Long Noncoding 0

Types de publication

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.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2633-2648.e19

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL109512
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008150
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH107666
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS105604
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109905
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH106842
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124486
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134817
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125244
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135313
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007057
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009431
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139478
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142015
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG009916
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM007033
Pays : United States
Organisme : NHLBI NIH HHS
ID : R33 HL120757
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142028
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010067
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066490
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122924
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG009494
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101822
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201000029C
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101814
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States

Investigateurs

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

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests F.A. is an inventor on a patent application related to TensorQTL; S.E.C. is a co-founder and chief technology officer at Variant Bio and owns stock in Variant Bio; T.L. is on the scientific advisory board of Variant Bio, Goldfinch Bio, and GSK and owns stock in Variant Bio; and S.B.M. is on the scientific advisory board of MyOme. All other authors report no competing interests.

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Auteurs

Olivia M de Goede (OM)

Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: odegoede@stanford.edu.

Daniel C Nachun (DC)

Department of Pathology, Stanford University, Stanford, CA 94305, USA.

Nicole M Ferraro (NM)

Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA.

Michael J Gloudemans (MJ)

Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA.

Abhiram S Rao (AS)

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

Craig Smail (C)

Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO 64108, USA.

Tiffany Y Eulalio (TY)

Biomedical Informatics Training Program, Stanford University, Stanford, CA 94305, USA.

François Aguet (F)

The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Bernard Ng (B)

Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC V5Z 4H4, Canada.

Jishu Xu (J)

Rush Alzheimer's Disease Center, Rush University, Chicago, Illinois 60612, USA.

Alvaro N Barbeira (AN)

Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Stephane E Castel (SE)

New York Genome Center, New York, NY 10013, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.

Sarah Kim-Hellmuth (S)

New York Genome Center, New York, NY 10013, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich, Munich 80337, Germany.

YoSon Park (Y)

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.

Alexandra J Scott (AJ)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.

Benjamin J Strober (BJ)

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

Christopher D Brown (CD)

Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.

Xiaoquan Wen (X)

Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.

Ira M Hall (IM)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

Alexis Battle (A)

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA.

Tuuli Lappalainen (T)

New York Genome Center, New York, NY 10013, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.

Hae Kyung Im (HK)

Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Kristin G Ardlie (KG)

The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Sara Mostafavi (S)

Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.

Thomas Quertermous (T)

Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.

Karla Kirkegaard (K)

Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

Stephen B Montgomery (SB)

Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: smontgom@stanford.edu.

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Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Maladie des artères coronaires › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Diabète de type 1 › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Maladie › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Phénomènes physiologiques › Spécificité d'organe › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Caractéristiques de la population › Population › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › ARN long non codant › Population-scale tissue transcriptomics maps...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Population-scale tissue transcriptomics maps...