The role of DNA methylation in the aetiology of anxiety proneness in a cohort of South African adolescents: an exploratory study

[摘要] ENGLISH ABSTRACT: Anxiety disorders are a range of complex disorders characterised by abnormal anxiety in theabsence of anxiety-provoking stimuli. The aetiology of anxiety disorders is attributed tointeraction between genetic and environmental factors. It is crucial to identify and characteriserisk factors that result in the development of anxiety disorders in adulthood. Anxiety proneness(AP) is one such risk factor and represents an endophenotype for anxiety disorders. Severalstudies have previously associated hypothalamic- pituitary- adrenal (HPA) axis related geneswith anxiety disorder development, however these studies generally do not account forenvironmental contributors. Epigenetics provides a mechanism to study environment and geneinteraction. DNA methylation is a well-studied epigenetic modification with the ability toinfluence gene expression. The present study aimed to investigate the role that genome-widealterations in DNA methylation play in the development of AP by investigating South Africanadolescents who have experienced differing levels of childhood trauma (n = 63). The IlluminaHumanMethylation450K BeadChip array was used to conduct genome-wide DNA methylation analysis on 46 individuals. EpiTYPER MassARRAY technology was used to verify selecteddifferentially methylated genes from the initial analysis, as well as to analyse additional HPAaxisrelated genes. Several genes were found to be differentially methylated prior to correctionfor multiple testing, and the majority of these had designated brain functions. Additionally, asignificant trend in methylation was observed in the promoter region of the serotonintransporter gene (SLC6A4). In conclusion, the current study indicates a role for the methylationof SLC6A4 in the development of AP in South African adolescents, however these results needto be replicated in a larger study sample.

[发布机构] Stellenbosch University