The GTEx Consortium atlas of genetic regulatory effects across human tissues

The GTEx Consortium

doi:10.1126/SCIENCE.AAZ1776

The GTEx Consortium atlas of genetic regulatory effects across human tissues

The GTEx Consortium

Family Medicine

The Broad Institute of MIT and Harvard
The University of Chicago
University of Geneva
University of Dundee
New York Genome Cente
Columbia University
Princeton University
Max Planck Institute of Psychiatry
Johns Hopkins University
Stanford University
Vanderbilt University
University of Cambridge
MRC Epidemiology Unit
Harvard University
Scripps Research Translational Institute
Scripps Research Institute
Barcelona Biomedical Research Park
Polytechnic University of Catalonia
University of Pennsylvania
University of Michigan, Ann Arbor
Swiss Institute of Bioinformatics
Massachusetts General Hospital Cancer Center
Pompeu Fabra University
Massachusetts General Hospital
Northwestern University

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

3740 Scopus citations

Abstract

The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

Original language	English
Pages (from-to)	1318-1330
Number of pages	13
Journal	Science
Volume	369
Issue number	6509
DOIs	https://doi.org/10.1126/SCIENCE.AAZ1776
State	Published - Sep 1 2020

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10.1126/SCIENCE.AAZ1776

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@article{4e1cb6b34f724031889689e8030c76ba,

title = "The GTEx Consortium atlas of genetic regulatory effects across human tissues",

abstract = "The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.",

author = "\{The GTEx Consortium\} and Fran{\c c}ois Aguet and Barbeira, \{Alvaro N.\} and Rodrigo Bonazzola and Andrew Brown and Castel, \{Stephane E.\} and Brian Jo and Silva Kasela and Sarah Kim-Hellmuth and Yanyu Liang and Meritxell Oliva and Flynn, \{Elise D.\} and Princy Parsana and Laure Fresard and Gamazon, \{Eric R.\} and Hamel, \{Andrew R.\} and Yuan He and Farhad Hormozdiari and Pejman Mohammadi and Manuel Mu{\~n}oz-Aguirre and Park, \{Yo Son\} and Ashis Saha and Segr{\`e}, \{Ayellet V.\} and Strober, \{Benjamin J.\} and Xiaoquan Wen and Valentin Wucher and Ardlie, \{Kristin G.\} and Alexis Battle and Brown, \{Christopher D.\} and Nancy Cox and Sayantan Das and Dermitzakis, \{Emmanouil T.\} and Engelhardt, \{Barbara E.\} and Diego Garrido-Mart{\'i}n and Gay, \{Nicole R.\} and Getz, \{Gad A.\} and Roderic Guig{\'o} and Handsaker, \{Robert E.\} and Hoffman, \{Paul J.\} and Im, \{Hae Kyung\} and Seva Kashin and Alan Kwong and Tuuli Lappalainen and Xiao Li and MacArthur, \{Daniel G.\} and Montgomery, \{Stephen B.\} and Rouhana, \{John M.\} and Matthew Stephens and Stranger, \{Barbara E.\} and Ellen Todres and Gardiner, \{Heather M.\}",

year = "2020",

month = sep,

day = "1",

doi = "10.1126/SCIENCE.AAZ1776",

language = "English",

volume = "369",

pages = "1318--1330",

journal = "Science",

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publisher = "American Association for the Advancement of Science",

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T1 - The GTEx Consortium atlas of genetic regulatory effects across human tissues

AU - The GTEx Consortium

AU - Aguet, François

AU - Barbeira, Alvaro N.

AU - Bonazzola, Rodrigo

AU - Brown, Andrew

AU - Castel, Stephane E.

AU - Jo, Brian

AU - Kasela, Silva

AU - Kim-Hellmuth, Sarah

AU - Liang, Yanyu

AU - Oliva, Meritxell

AU - Flynn, Elise D.

AU - Parsana, Princy

AU - Fresard, Laure

AU - Gamazon, Eric R.

AU - Hamel, Andrew R.

AU - He, Yuan

AU - Hormozdiari, Farhad

AU - Mohammadi, Pejman

AU - Muñoz-Aguirre, Manuel

AU - Park, Yo Son

AU - Saha, Ashis

AU - Segrè, Ayellet V.

AU - Strober, Benjamin J.

AU - Wen, Xiaoquan

AU - Wucher, Valentin

AU - Ardlie, Kristin G.

AU - Battle, Alexis

AU - Brown, Christopher D.

AU - Cox, Nancy

AU - Das, Sayantan

AU - Dermitzakis, Emmanouil T.

AU - Engelhardt, Barbara E.

AU - Garrido-Martín, Diego

AU - Gay, Nicole R.

AU - Getz, Gad A.

AU - Guigó, Roderic

AU - Handsaker, Robert E.

AU - Hoffman, Paul J.

AU - Im, Hae Kyung

AU - Kashin, Seva

AU - Kwong, Alan

AU - Lappalainen, Tuuli

AU - Li, Xiao

AU - MacArthur, Daniel G.

AU - Montgomery, Stephen B.

AU - Rouhana, John M.

AU - Stephens, Matthew

AU - Stranger, Barbara E.

AU - Todres, Ellen

AU - Gardiner, Heather M.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

AB - The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

UR - https://www.scopus.com/pages/publications/85090818998

U2 - 10.1126/SCIENCE.AAZ1776

DO - 10.1126/SCIENCE.AAZ1776

M3 - Article

C2 - 32913098

AN - SCOPUS:85090818998

SN - 0036-8075

VL - 369

SP - 1318

EP - 1330

JO - Science

JF - Science

IS - 6509

ER -

The GTEx Consortium atlas of genetic regulatory effects across human tissues

Abstract

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