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PMID |
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TITLE |
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Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
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LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Cuellar Partida G |
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Cuellar Partida |
Gabriel |
G |
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University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. |
Laurin C |
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Laurin |
Charles |
C |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Ring SM |
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Ring |
Susan M |
SM |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Gaunt TR |
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Gaunt |
Tom R |
TR |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
McRae A |
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McRae |
Allan |
A |
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The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. |
Visscher PM |
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Visscher |
Peter M |
PM |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Montgomery G |
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Montgomery |
Grant |
G |
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The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Hemani G |
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Hemani |
Gibran |
G |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Suderman M |
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Suderman |
Matthew |
M |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Relton CL |
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Relton |
Caroline L |
CL |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Davey Smith G |
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Davey Smith |
George |
G |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
Evans DM |
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Evans |
David M |
DM |
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Medical Research Council (MRC) Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. |
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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 |
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MEDLINE JOURNAL |
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MEDLINETA: Hum Mol Genet |
COUNTRY: England |
ISSNLINKING: 0964-6906 |
NLMUNIQUEID: 9208958 |
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Journal Article |
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