The GTEx Consortium atlas of genetic regulatory effects across human tissues.

TitleThe GTEx Consortium atlas of genetic regulatory effects across human tissues.
Publication TypeJournal Article
Year of Publication2020
Corporate AuthorsGTEx Consortium
JournalScience
Volume369
Issue6509
Pagination1318-1330
Date Published2020 09 11
ISSN1095-9203
KeywordsDatasets as Topic, Disease, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Male, Organ Specificity, Quantitative Trait Loci, Sequence Analysis, RNA
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.

DOI10.1126/science.aaz1776
Alternate JournalScience
PubMed ID32913098
PubMed Central IDPMC7737656
Grant ListR01 CA229618 / CA / NCI NIH HHS / United States
R01 MH107666 / MH / NIMH NIH HHS / United States
R01 MH106842 / MH / NIMH NIH HHS / United States
K99 HG009916 / HG / NHGRI NIH HHS / United States
R01 HL142028 / HL / NHLBI NIH HHS / United States
R01 HG006855 / HG / NHGRI NIH HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
UL1 TR002550 / TR / NCATS NIH HHS / United States
R01 HG011138 / HG / NHGRI NIH HHS / United States
U01 MH104393 / MH / NIMH NIH HHS / United States
R01 HG010480 / HG / NHGRI NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
U41 HG002371 / HG / NHGRI NIH HHS / United States
R01 HG008150 / HG / NHGRI NIH HHS / United States
R01 MH109905 / MH / NIMH NIH HHS / United States
F31 HG010580 / HG / NHGRI NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States
U01 HG007593 / HG / NHGRI NIH HHS / United States
R01 GM124486 / GM / NIGMS NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
U01 HG007598 / HG / NHGRI NIH HHS / United States
R01 AG057422 / AG / NIA NIH HHS / United States
T32 DK110919 / DK / NIDDK NIH HHS / United States
R01 HG002585 / HG / NHGRI NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
R01 HG010731 / HG / NHGRI NIH HHS / United States
F32 HG009987 / HG / NHGRI NIH HHS / United States
R01 HG010067 / HG / NHGRI NIH HHS / United States
R01 MH090941 / MH / NIMH 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
HHSN261200800001C / RC / CCR NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
R35 HG010718 / HG / NHGRI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States