Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Nat Commun. 2019 Mar 27;10(1):1383. doi: 10.1038/s41467-019-09301-y.

Abstract

Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CpG Islands
  • DNA Methylation / genetics*
  • Female
  • Gene Expression Regulation*
  • Genomic Imprinting / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci / genetics*
  • Scotland