Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans

Gabriel Cuellar-Partida, Charles Laurin, Susan Ring, Tom Gaunt, Allan McRae, Peter M. Visscher, Grant Montgomery, Nicholas G Martin, Gibran Hemani, Matthew Suderman, Caroline Relton, George Davey Smith, David Evans

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)
295 Downloads (Pure)


Genomic imprinting is an epigenetic mechanism leading to parent-of-origin silencing of alleles. So far, the precise number of imprinted regions in humans is uncertain. In this study, we leveraged genome-wide DNA methylation in whole blood measured longitudinally at three time points (birth, childhood and adolescence) and genome-wide association studies (GWAS) data in 740 mother–child duos from the Avon Longitudinal Study of parents and children to identify candidate imprinted loci. We reasoned that cis-meQTLs at genomic regions that were imprinted would show strong evidence of parent-of-origin associations with DNA methylation, enabling the detection of imprinted regions. Using this approach, we identified genome-wide significant cis-meQTLs that exhibited parent-of-origin effects (POEs) at 82 loci, 34 novel and 48 regions previously implicated in imprinting (3.7−10<P < 10−300). Using an independent dataset from the Brisbane Systems Genetic Study, we replicated 76 out of the 82 identified loci. POEs were remarkably consistent across time points and were so strong at some loci that methylation levels enabled good discrimination of parental transmissions at these and surrounding genomic regions. The implication is that parental allelic transmissions could be modelled at many imprinted (and linked) loci in GWAS of unrelated individuals given a combination of genetic and methylation data. Novel regions showing parent of origin effects on methylation will require replication using a different technology and further functional experiments to confirm that such effects arise through a genomic imprinting mechanism.
Original languageEnglish
Pages (from-to)2927-2939
Number of pages13
JournalHuman Molecular Genetics
Issue number16
Early online date1 Jun 2018
Publication statusPublished - Aug 2018


Dive into the research topics of 'Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans'. Together they form a unique fingerprint.

Cite this