Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
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.
Duke Scholars
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Related Subject Headings
- Transcriptome
- Quantitative Trait, Heritable
- Quantitative Trait Loci
- Polymorphism, Single Nucleotide
- Multifactorial Inheritance
- Humans
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Gene Expression Regulation
- Epigenesis, Genetic
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Transcriptome
- Quantitative Trait, Heritable
- Quantitative Trait Loci
- Polymorphism, Single Nucleotide
- Multifactorial Inheritance
- Humans
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Gene Expression Regulation
- Epigenesis, Genetic