Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 08 2019
23 08 2019
Historique:
received:
14
06
2019
accepted:
05
08
2019
entrez:
25
8
2019
pubmed:
25
8
2019
medline:
27
12
2019
Statut:
epublish
Résumé
Transcriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we generate a small but significant improvement in the accuracy of transcriptome prediction and increase the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge on biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify compounds that mimic, or reverse, trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.
Identifiants
pubmed: 31444360
doi: 10.1038/s41467-019-11874-7
pii: 10.1038/s41467-019-11874-7
pmc: PMC6707297
doi:
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
3834Subventions
Organisme : NIMH NIH HHS
ID : R01 MH109897
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050986
Pays : United States
Organisme : BLRD VA
ID : I01 BX004189
Pays : United States
Organisme : BLRD VA
ID : I01 BX002395
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH096890
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
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