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dc.contributor.authorBell, JT
dc.contributor.authorTsai, P-C
dc.contributor.authorYang, T-P
dc.contributor.authorPidsley, R
dc.contributor.authorNisbet, J
dc.contributor.authorGlass, D
dc.contributor.authorMangino, M
dc.contributor.authorZhai, G
dc.contributor.authorZhang, F
dc.contributor.authorValdes, A
dc.contributor.authorShin, S-Y
dc.contributor.authorDempster, EL
dc.contributor.authorMurray, RM
dc.contributor.authorGrundberg, E
dc.contributor.authorHedman, AK
dc.contributor.authorNica, A
dc.contributor.authorSmall, KS
dc.contributor.authorMuTHER Consortium,
dc.contributor.authorDermitzakis, ET
dc.contributor.authorMcCarthy, MI
dc.contributor.authorMill, J
dc.contributor.authorSpector, TD
dc.contributor.authorDeloukas, P
dc.date.accessioned2020-12-17T04:28:27Z
dc.date.available2020-12-17T04:28:27Z
dc.date.issued2012
dc.identifierpii: PGENETICS-D-11-02398
dc.identifier.citationBell, J. T., Tsai, P. -C., Yang, T. -P., Pidsley, R., Nisbet, J., Glass, D., Mangino, M., Zhai, G., Zhang, F., Valdes, A., Shin, S. -Y., Dempster, E. L., Murray, R. M., Grundberg, E., Hedman, A. K., Nica, A., Small, K. S., MuTHER Consortium, , Dermitzakis, E. T. ,... Deloukas, P. (2012). Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population.. PLoS Genet, 8 (4), pp.e1002629-. https://doi.org/10.1371/journal.pgen.1002629.
dc.identifier.issn1553-7390
dc.identifier.urihttp://hdl.handle.net/11343/255325
dc.description.abstractAge-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes. Twin-based DNA methylation levels at 26,690 CpG-sites showed evidence for mean genome-wide heritability of 18%, which was supported by the identification of 1,537 CpG-sites with methylation QTLs in cis at FDR 5%. We performed genome-wide analyses to discover differentially methylated regions (DMRs) for sixteen age-related phenotypes (ap-DMRs) and chronological age (a-DMRs). Epigenome-wide association scans (EWAS) identified age-related phenotype DMRs (ap-DMRs) associated with LDL (STAT5A), lung function (WT1), and maternal longevity (ARL4A, TBX20). In contrast, EWAS for chronological age identified hundreds of predominantly hyper-methylated age DMRs (490 a-DMRs at FDR 5%), of which only one (TBX20) was also associated with an age-related phenotype. Therefore, the majority of age-related changes in DNA methylation are not associated with phenotypic measures of healthy ageing in later life. We replicated a large proportion of a-DMRs in a sample of 44 younger adult MZ twins aged 20 to 61, suggesting that a-DMRs may initiate at an earlier age. We next explored potential genetic and environmental mechanisms underlying a-DMRs and ap-DMRs. Genome-wide overlap across cis-meQTLs, genotype-phenotype associations, and EWAS ap-DMRs identified CpG-sites that had cis-meQTLs with evidence for genotype-phenotype association, where the CpG-site was also an ap-DMR for the same phenotype. Monozygotic twin methylation difference analyses identified one potential environmentally-mediated ap-DMR associated with total cholesterol and LDL (CSMD1). Our results suggest that in a small set of genes DNA methylation may be a candidate mechanism of mediating not only environmental, but also genetic effects on age-related phenotypes.
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEpigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population.
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1002629
melbourne.affiliation.departmentMedical Education
melbourne.source.titlePLoS Genetics
melbourne.source.volume8
melbourne.source.issue4
melbourne.source.pagese1002629-
dc.rights.licenseCC BY
melbourne.elementsid1334603
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330116
melbourne.contributor.authorMurray, Robin
dc.identifier.eissn1553-7404
melbourne.accessrightsOpen Access


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