dc.contributor.advisor |
Walker, Caroline |
|
dc.contributor.advisor |
Snell, Russell |
|
dc.contributor.author |
O'Donnell, Erin |
|
dc.date.accessioned |
2021-06-17T20:41:32Z |
|
dc.date.available |
2021-06-17T20:41:32Z |
|
dc.date.issued |
2021 |
en |
dc.identifier.uri |
https://hdl.handle.net/2292/55339 |
|
dc.description |
Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Early life adversity can have long term consequences on wellbeing, including an increased
risk of childhood depression. One mechanism proposed for this association is epigenetic
modifications. These effects may be mediated by changes in DNA methylation at genes
affecting disease predisposition. Methylation of the glucocorticoid receptor (NR3C1), a stress
response gene, has been associated with depression. It is hypothesised that DNA methylation
may mediate the effect due to early life adversity resulting in depression in New Zealand
children.
This study was undertaken using data from the longitudinal study Growing Up in New
Zealand. The association between adversity and depression was investigated using the full
cohort of 6953 children. Methylation of the NR3C1 locus was investigated in a 766
participant subset and a pilot genome-wide methylation investigation in 58 Māori
participants. Maternal, family and neighbourhood stressors were reported on during
pregnancy and at nine months post-natal and analysed in a cumulative design. Depression
was measured at age eight years using the Centre for Epidemiologic Studies Depression Scale
(CES-DC). DNA methylation was assayed in DNA extracted from saliva collected at age 4.5
years. The NR3C1 candidate gene subset was assayed with the EPITYPER and the genome
wide pilot was assayed on EPIC chips.
Adversity was found to be associated with increased risk of depression symptoms across both
the full cohort (1.2 fold increase, p-value = 4.01e-06) and within the subset selected for
NR3C1 DNA methylation assessment (1.16 fold increase, p-value = 0.016). The data from
the EPITYPER array, which was undertaken by a service provider, had significant quality
issues which were uncovered after considerable investigation. The pilot EPIC chip analysis
revealed 12 CpG sites differentially methylated by depression phenotypes. 11 of these sites
likely included common polymorphisms, and it remains to be determined if the DNA
variation or methylation are the underlying mechanistic link. Excitingly, the remaining CpG
site resides within the ERGIC1 gene, previously found to be associated with various
neurological conditions.
This is the first study to assess early life adversity and depression in NZ children, providing
evidence that early life adversity is linked to poor outcomes in early life. The EPIC chip
approach was a technical success revealing epigenetic-genetic associations with child
depression suggesting a larger study is warranted. |
|
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA |
en |
dc.rights |
Restricted Item. Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
|
dc.title |
DNA Methylation Mediates the Association Between Early Life Adversity and Childhood Depression |
|
dc.type |
Thesis |
en |
thesis.degree.discipline |
Biological Sciences |
|
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.date.updated |
2021-06-13T03:23:11Z |
|
dc.rights.holder |
Copyright: the author |
en |
dc.identifier.wikidata |
Q112956273 |
|