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
24887635
TITLE
Contribution of genetic variation to transgenerational inheritance of DNA methylation.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations.
RESULTS NlmCategory: RESULTS
The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
CONCLUSIONS NlmCategory: CONCLUSIONS
The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.
DATE PUBLISHED
2014
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/11/04
accepted 2014/05/29
aheadofprint 2014/05/29
entrez 2014/06/03 06:00
pubmed 2014/06/03 06:00
medline 2014/06/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
McRae AF McRae Allan F AF
Powell JE Powell Joseph E JE
Henders AK Henders Anjali K AK
Bowdler L Bowdler Lisa L
Hemani G Hemani Gibran G
Shah S Shah Sonia S
Painter JN Painter Jodie N JN
Martin NG Martin Nicholas G NG
Visscher PM Visscher Peter M PM
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 15
ISSUE: 5
TITLE: Genome biology
ISOABBREVIATION: Genome Biol.
YEAR: 2014
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1465-6914
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genome Biol
COUNTRY: England
ISSNLINKING: 1474-7596
NLMUNIQUEID: 100960660
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
GM057091 NIGMS NIH HHS United States
GM099568 NIGMS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC4072933 NLM