Genetic effects on promoter usage are highly context-specific and contribute to complex traits.
RNA-seq
computational biology
genetics
genomics
human
macrophages
splicing
systems biology
transcription
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
08 01 2019
08 01 2019
Historique:
received:
05
09
2018
accepted:
08
01
2019
pubmed:
9
1
2019
medline:
11
4
2020
entrez:
9
1
2019
Statut:
epublish
Résumé
Genetic variants regulating RNA splicing and transcript usage have been implicated in both common and rare diseases. Although transcript usage quantitative trait loci (tuQTLs) have been mapped across multiple cell types and contexts, it is challenging to distinguish between the main molecular mechanisms controlling transcript usage: promoter choice, splicing and 3' end choice. Here, we analysed RNA-seq data from human macrophages exposed to three inflammatory and one metabolic stimulus. In addition to conventional gene-level and transcript-level analyses, we also directly quantified promoter usage, splicing and 3' end usage. We found that promoters, splicing and 3' ends were predominantly controlled by independent genetic variants enriched in distinct genomic features. Promoter usage QTLs were also 50% more likely to be context-specific than other tuQTLs and constituted 25% of the transcript-level colocalisations with complex traits. Thus, promoter usage might be an underappreciated molecular mechanism mediating complex trait associations in a context-specific manner.
Identifiants
pubmed: 30618377
doi: 10.7554/eLife.41673
pii: 41673
pmc: PMC6349408
doi:
pii:
Substances chimiques
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : Wellcome
ID : WT098503
Pays : International
Organisme : Estonian Research Council
ID : MOBJD67
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Estonian Research Council
ID : IUT34-4
Pays : International
Organisme : British Heart Foundation Cambridge Centre of Excellence
ID : RE/13/6/30180
Pays : International
Organisme : Wellcome
ID : WT09805
Pays : International
Organisme : Wellcome
ID : WT099754/Z/12/Z
Pays : International
Informations de copyright
© 2019, Alasoo et al.
Déclaration de conflit d'intérêts
KA, JR, JD, DP, DG No competing interests declared, DF Since October 2015, Daniel F Freitag has been a full-time employee of Bayer AG, Germany
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