Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
29860447
TITLE
Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans.
ABSTRACT
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 3 time points (birth, childhood and adolescence) and 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 data set 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.
DATE PUBLISHED
2018 Jun 01
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/03/26
accepted 2018/05/23
entrez 2018/06/04 06:00
pubmed 2018/06/04 06:00
medline 2018/06/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cuellar Partida G Cuellar Partida Gabriel G University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
Laurin C Laurin Charles C Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Ring SM Ring Susan M SM Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Gaunt TR Gaunt Tom R TR Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
McRae A McRae Allan A The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Visscher PM Visscher Peter M PM Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Montgomery G Montgomery Grant G The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Hemani G Hemani Gibran G Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Suderman M Suderman Matthew M Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Relton CL Relton Caroline L CL Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Davey Smith G Davey Smith George G Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Evans DM Evans David M DM Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2018
MONTH: Jun
DAY: 01
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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