Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

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BIOS Consortium , Min , J L , Hemani , G , Hannon , E , Kumar , A , Gupta , R , Bollepalli , S , Mandaviya , P , Ollikainen , M , Kaprio , J & Lahti , J 2021 , ' Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation ' , Nature Genetics , vol. 53 , no. 9 , pp. 1311-+ .

Title: Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Author: BIOS Consortium; Min, Josine L.; Hemani, Gibran; Hannon, Eilis; Kumar, Ashish; Gupta, Richa; Bollepalli, Sailalitha; Mandaviya, Pooja; Ollikainen, Miina; Kaprio, Jaakko; Lahti, Jari
Contributor organization: Helsinki Institute of Life Science HiLIFE
Institute for Molecular Medicine Finland
Epigenetics of Complex Diseases and Traits
Department of Public Health
Department of Psychology and Logopedics
Date: 2021-09
Language: eng
Number of pages: 26
Belongs to series: Nature Genetics
ISSN: 1061-4036
Abstract: DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs. 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.
3111 Biomedicine
Peer reviewed: Yes
Rights: other
Usage restriction: openAccess
Self-archived version: acceptedVersion

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