Extensive variation and low heritability of DNA methylation identified in a twin study.

Abstract:

:Disturbance of DNA methylation leading to aberrant gene expression has been implicated in the etiology of many diseases. Whereas variation at the genetic level has been studied extensively, less is known about the extent and function of epigenetic variation. To explore variation and heritability of DNA methylation, we performed bisulfite sequencing of 1760 CpG sites in 186 regions in the human major histocompatibility complex (MHC) in CD4+ lymphocytes from 49 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs. Individuals show extensive variation in DNA methylation both between and within regions. In addition, many regions also have a complex pattern of variation. Globally, there appears to be a bimodal distribution of DNA methylation in the regions, but a significant fraction of the CpG sites are also heterogeneously methylated. Classification of regions into CpG islands (intragenic and intergenic), 5' end of genes not associated with a defined CpG island, conserved noncoding regions, and random CpG sites shows region-type differences in variation and heritability. Analyses revealed slightly lower intra-pair differences among MZ than among DZ pairs, suggesting some genetic influences on DNA methylation variation, with most of the variance attributed to nongenetic factors. Overall, heritability estimates of DNA methylation were low. Our heritability estimates are, however, somewhat deflated due to the presence of batch effects that artificially inflate the estimates of shared environment.

journal_name

Genome Res

journal_title

Genome research

authors

Gervin K,Hammerø M,Akselsen HE,Moe R,Nygård H,Brandt I,Gjessing HK,Harris JR,Undlien DE,Lyle R

doi

10.1101/gr.119685.110

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

1813-21

issue

11

eissn

1088-9051

issn

1549-5469

pii

gr.119685.110

journal_volume

21

pub_type

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