Imputed gene associations identify replicable trans-acting genes enriched in transcription pathways and complex traits.
complex trait genetics
gene expression
genetic prediction
trans-eQTL
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
13
11
2018
revised:
15
02
2019
accepted:
18
03
2019
pubmed:
6
4
2019
medline:
15
11
2019
entrez:
6
4
2019
Statut:
ppublish
Résumé
Regulation of gene expression is an important mechanism through which genetic variation can affect complex traits. A substantial portion of gene expression variation can be explained by both local (cis) and distal (trans) genetic variation. Much progress has been made in uncovering cis-acting expression quantitative trait loci (cis-eQTL), but trans-eQTL have been more difficult to identify and replicate. Here we take advantage of our ability to predict the cis component of gene expression coupled with gene mapping methods such as PrediXcan to identify high confidence candidate trans-acting genes and their targets. That is, we correlate the cis component of gene expression with observed expression of genes in different chromosomes. Leveraging the shared cis-acting regulation across tissues, we combine the evidence of association across all available Genotype-Tissue Expression Project tissues and find 2,356 trans-acting/target gene pairs with high mappability scores. Reassuringly, trans-acting genes are enriched in transcription and nucleic acid binding pathways and target genes are enriched in known transcription factor binding sites. Interestingly, trans-acting genes are more significantly associated with selected complex traits and diseases than target or background genes, consistent with percolating trans effects. Our scripts and summary statistics are publicly available for future studies of trans-acting gene regulation.
Identifiants
pubmed: 30950127
doi: 10.1002/gepi.22205
pmc: PMC6687523
mid: NIHMS1020131
doi:
Substances chimiques
Trans-Activators
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
596-608Subventions
Organisme : NIMH NIH HHS
ID : R01 MH107666
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109905
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30DK20595
Pays : United States
Organisme : NHGRI NIH HHS
ID : R15 HG009569
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Informations de copyright
© 2019 The Authors. Genetic Epidemiology Published by Wiley Periodicals, Inc.
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