Sökning: WFRF:(Bell Jordana T.) > (2011-2014) > Epigenome-wide scan...
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000 | 04013naa a2200517 4500 | |
001 | oai:DiVA.org:uu-275694 | |
003 | SwePub | |
008 | 160204s2012 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2756942 URI |
024 | 7 | a https://doi.org/10.1371/journal.pgen.10026292 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Bell, Jordana T4 aut |
245 | 1 0 | a Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. |
264 | c 2012-04-19 | |
264 | 1 | b Public Library of Science (PLoS),c 2012 |
338 | a print2 rdacarrier | |
520 | a Age-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. | |
700 | 1 | a Tsai, Pei-Chien4 aut |
700 | 1 | a Yang, Tsun-Po4 aut |
700 | 1 | a Pidsley, Ruth4 aut |
700 | 1 | a Nisbet, James4 aut |
700 | 1 | a Glass, Daniel4 aut |
700 | 1 | a Mangino, Massimo4 aut |
700 | 1 | a Zhai, Guangju4 aut |
700 | 1 | a Zhang, Feng4 aut |
700 | 1 | a Valdes, Ana4 aut |
700 | 1 | a Shin, So-Youn4 aut |
700 | 1 | a Dempster, Emma L4 aut |
700 | 1 | a Murray, Robin M4 aut |
700 | 1 | a Grundberg, Elin4 aut |
700 | 1 | a Hedman, Asa K4 aut |
700 | 1 | a Nica, Alexandra4 aut |
700 | 1 | a Small, Kerrin S4 aut |
700 | 1 | a Dermitzakis, Emmanouil T4 aut |
700 | 1 | a McCarthy, Mark I4 aut |
700 | 1 | a Mill, Jonathan4 aut |
700 | 1 | a Spector, Tim D4 aut |
700 | 1 | a Deloukas, Panos4 aut |
773 | 0 | t PLOS Geneticsd : Public Library of Science (PLoS)g 8:4q 8:4x 1553-7390x 1553-7404 |
856 | 4 | u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002629&type=printable |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-275694 |
856 | 4 8 | u https://doi.org/10.1371/journal.pgen.1002629 |
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