Browsing by Author "Zass, Lyndon"

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    The role of DNA methylation in the aetiology of anxiety proneness in a cohort of South African adolescents: an exploratory study
    (Stellenbosch : Stellenbosch University, 2017-03) Zass, Lyndon; Hemmings, Sian; Seedat, Soraya; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: Anxiety disorders are a range of complex disorders characterised by abnormal anxiety in the absence of anxiety-provoking stimuli. The aetiology of anxiety disorders is attributed to interaction between genetic and environmental factors. It is crucial to identify and characterise risk 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. Several studies have previously associated hypothalamic- pituitary- adrenal (HPA) axis related genes with anxiety disorder development, however these studies generally do not account for environmental contributors. Epigenetics provides a mechanism to study environment and gene interaction. DNA methylation is a well-studied epigenetic modification with the ability to influence gene expression. The present study aimed to investigate the role that genome-wide alterations in DNA methylation play in the development of AP by investigating South African adolescents who have experienced differing levels of childhood trauma (n = 63). The Illumina HumanMethylation450K BeadChip array was used to conduct genome-wide DNA methylation analysis on 46 individuals. EpiTYPER MassARRAY technology was used to verify selected differentially methylated genes from the initial analysis, as well as to analyse additional HPAaxis related genes. Several genes were found to be differentially methylated prior to correction for multiple testing, and the majority of these had designated brain functions. Additionally, a significant trend in methylation was observed in the promoter region of the serotonin transporter gene (SLC6A4). In conclusion, the current study indicates a role for the methylation of SLC6A4 in the development of AP in South African adolescents, however these results need to be replicated in a larger study sample.