dc.contributor.author |
Horvath, S |
en |
dc.contributor.author |
Langfelder, P |
en |
dc.contributor.author |
Kwak, S |
en |
dc.contributor.author |
Aaronson, J |
en |
dc.contributor.author |
Rosinski, J |
en |
dc.contributor.author |
Vogt, TF |
en |
dc.contributor.author |
Eszes, M |
en |
dc.contributor.author |
Faull, Richard |
en |
dc.contributor.author |
Curtis, Maurice |
en |
dc.contributor.author |
Waldvogel, Henry |
en |
dc.contributor.author |
Choi, O-W |
en |
dc.contributor.author |
Tung, S |
en |
dc.contributor.author |
Vinters, HV |
en |
dc.contributor.author |
Coppola, G |
en |
dc.contributor.author |
Yang, XW |
en |
dc.date.accessioned |
2017-09-06T23:08:34Z |
en |
dc.date.issued |
2016-07-27 |
en |
dc.identifier.citation |
Aging 8(7):1485-1512 27 Jul 2016 |
en |
dc.identifier.issn |
1945-4589 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/35531 |
en |
dc.description.abstract |
Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. |
en |
dc.format.medium |
Print |
en |
dc.language |
eng |
en |
dc.publisher |
Impact Journals |
en |
dc.relation.ispartofseries |
Aging |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1945-4589/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/3.0/ |
en |
dc.title |
Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.18632/aging.101005 |
en |
pubs.issue |
7 |
en |
pubs.begin-page |
1485 |
en |
pubs.volume |
8 |
en |
dc.description.version |
VoR - Version of Record |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
27479945 |
en |
pubs.end-page |
1512 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
538082 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
en |
dc.identifier.eissn |
1945-4589 |
en |
pubs.record-created-at-source-date |
2017-09-07 |
en |
pubs.dimensions-id |
27479945 |
en |