Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control.
CoRSIV
DNA methylation
DOHaD
Epigenetic epidemiology
Epigenome-wide association study
Genetics
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
12 01 2023
12 01 2023
Historique:
received:
04
08
2022
accepted:
01
12
2022
entrez:
11
1
2023
pubmed:
12
1
2023
medline:
14
1
2023
Statut:
epublish
Résumé
Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition. We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease.
Sections du résumé
BACKGROUND
Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.
RESULTS
We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R
CONCLUSIONS
A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease.
Identifiants
pubmed: 36631879
doi: 10.1186/s13059-022-02827-3
pii: 10.1186/s13059-022-02827-3
pmc: PMC9835319
doi:
Substances chimiques
DNA Transposable Elements
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111522
Pays : United States
Organisme : NIH HHS
ID : S10 OD023469
Pays : United States
Informations de copyright
© 2022. The Author(s).
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