Cell type-specific genetic regulation of gene expression across human tissues.

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TitleCell type-specific genetic regulation of gene expression across human tissues.
Publication TypeJournal Article
Year of Publication2020
AuthorsKim-Hellmuth, S, Aguet, F, Oliva, M, Muñoz-Aguirre, M, Kasela, S, Wucher, V, Castel, SE, Hamel, AR, Viñuela, A, Roberts, AL, Mangul, S, Wen, X, Wang, G, Barbeira, AN, Garrido-Martín, D, Nadel, BB, Zou, Y, Bonazzola, R, Quan, J, Brown, A, Martinez-Perez, A, Soria, JManuel, Getz, G, Dermitzakis, ET, Small, KS, Stephens, M, Xi, HS, Im, HKyung, Guigo, R, Segrè, AV, Stranger, BE, Ardlie, KG, Lappalainen, T
Corporate AuthorsGTEx Consortium
JournalScience
Volume369
Issue6509
Date Published2020 09 11
ISSN1095-9203
KeywordsCells, Gene Expression Regulation, Humans, Organ Specificity, Quantitative Trait Loci, RNA, Long Noncoding, Transcriptome
Abstract

The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.
DOI10.1126/science.aaz8528
Alternate JournalScience
PubMed ID32913075
PubMed Central IDPMC8051643
Grant ListR01 CA229618 / CA / NCI NIH HHS / United States
U01 MH104393 / MH / NIMH NIH HHS / United States
R01 MH107666 / MH / NIMH NIH HHS / United States
R01 MH109905 / MH / NIMH NIH HHS / United States
R01 MH106842 / MH / NIMH NIH HHS / United States
U01 HG007598 / HG / NHGRI NIH HHS / United States
R01 HG002585 / HG / NHGRI NIH HHS / United States
K99 HG009916 / HG / NHGRI NIH HHS / United States
R01 HG006855 / HG / NHGRI NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
UL1 TR002550 / TR / NCATS 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
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
R01 HL142028 / HL / NHLBI NIH HHS / United States
MR/R023131/1 / MR / Medical Research Council / United Kingdom
R01 MH090951 / MH / NIMH NIH HHS / United States
MR/M004422/1 / MR / Medical Research Council / United Kingdom
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
R01 MH090937 / MH / NIMH NIH HHS / United States
T32 LM012424 / LM / NLM 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