Genomic And Phenomic Insights From An Atlas Of Genetic Effects On DNA Methylation

J.L. Min; G. Hemani; E. Hannon; K.F. Dekkers; K. Sugden; T.E. Moffitt; R. Poulton; A. Caspi; L. Arseneault; F. Gagnon; et al.

doi:10.1038/s41588-021-00923-x

Genomic And Phenomic Insights From An Atlas Of Genetic Effects On DNA Methylation

J.L. Min, G. Hemani, E. Hannon, K.F. Dekkers, K. Sugden, T.E. Moffitt, R. Poulton, A. Caspi, L. Arseneault, F. Gagnon, …

Nature Genetics, Vol.53, pp.1311-1321

2021

: https://doi.org/10.1038/s41588-021-00923-x

https://hdl.handle.net/10523/15960

genetic influences

DNA methylation (DNAm)

gene regulation and disease

DNAm quantitative trait locus (mQTL)

The full text of this article is freely and openly accessible from the following repository: https://pure.eur.nl/files/42372805/Genomic_and_phenotypic_insights_from_an_atlas_of_genetic_effects_on_DNA_methylation.pdf Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.

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https://rdcu.be/dYMrm

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: Genomic And Phenomic Insights From An Atlas Of Genetic Effects On DNA Methylation
: J.L. Min
G. Hemani
E. Hannon
K.F. Dekkers
K. Sugden
T.E. Moffitt
R. Poulton
A. Caspi
L. Arseneault
F. Gagnon
et al.
: Nature Genetics, Vol.53, pp.1311-1321
: Psychology; Dunedin Multidisciplinary Health and Development Research Unit (DMHDRU)
: Springer Science and Business Media LLC
: 2021
: 2021
: This item is not available in full-text via OUR Archive. Where available, a link to the published version is provided (check the DOI and/or the Files and links section). The full-text item may be open access on the publisher's website. Alternatively, readers may have subscription access to the full-text from the publisher. A link to a legal, open access version may be available - check the Abstract for this information. For all queries relating to the Dunedin Study, its research and publications, please email: dmhdru@otago.ac.nz
: English
: Journal article