| Title: | Parent of origin genetic effects on methylation in humans are common and influence complex trait variation |
| Journal: | Nature Communications |
| Published: | 27 Mar 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30918249/ |
| DOI: | https://doi.org/10.1038/s41467-019-09301-y |
| Citations: | 43 (7 in last 2 years) as of 8 Aug 2024 |
Publication 5512
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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.</p>
23 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
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