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

• DOI: 10.1038/s41467-019-09301-y
• Publication Date: 2019-03-27T16:49:55Z
• Authors: Yanni Zeng; Carmen Amador; Charley Xia; Riccardo Marioni; Duncan Sproul; Rosie M. Walker; Stewart W. Morris; Andrew Bretherick; Oriol Canela-Xandri; Thibaud S. Boutin; David W. Clark; Archie Campbell; Konrad Rawlik; Caroline Hayward; Reka Nagy; Albert Tenesa; David J. Porteous; James F. Wilson; Ian J. Deary; Kathryn L. Evans; Andrew M. McIntosh; Pau Navarro; Chris S. Haley
• Keywords: Trait; Genome-wide Association Study

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 potentially influenced by a false discovery rate ≤ 0.05 which 331 had not previously been identified. Cis and trans quantitative trait loci (mQTL) regulate variation through 54% (399/733) identified POE-influenced CpGs. The combined results provide strong evidence unidentified 171 loci. Methylation 14 associated with multiple metabolic traits. phenome-wide association analysis using mQTL SNPs imprinted locus waist circumference. These high resolution population-level map sites, their local distant regulators potential consequences complex