Genetic and epigenetic associations with child development and mental health in a South African birth cohort
type: CreativeWork
description: Childhood developmental and mental disorders – including internalising and externalising symptoms – are prevalent in low- and middle-income countries (LMICs) such as South Africa. There is growing interest in the associations between polygenic risk scores (PRS), epigenetic age (EA) deviation, DNA methylation risk scores (MRS), and key neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD). However, most work has thus far been undertaken in high-income countries (HICs) with participants of European ancestry; and populations of African ancestry have been notably under-represented. The Drakenstein Child Health Study (DCHS), an ongoing South African birth cohort study, provides an opportunity to investigate the associations of PRS, EA deviation, and MRS, with childhood developmental and mental health outcomes, in an ancestrally diverse study population. This doctoral project aimed to investigate potential genetic and epigenetic associations with adverse developmental and mental outcomes in children. This aim was addressed via five objectives. First, a systematic review was undertaken to collate existing work (both in HICs and LMICs) on associations between PRS (the weighted sum of risk alleles) and developmental and mental health disorders in childhood and adolescence. A second systematic review focused on associations between EA deviation (relative to chronological age) and the outcomes of interest. Third, empirical analyses of DCHS data investigated the relationship between a PRS for ADHD, and child developmental outcomes, as well as internalising and externalising symptoms. Fourth, the relationship between gestational EA deviation at birth, and child developmental and mental health outcomes in the DCHS, was explored. Finally, the association between MRS (the weighted sum of methylation markers' beta values) at birth, and the outcomes of interest, was investigated. The systematic reviews adhered to the Preferred Reporting Items for System…
abstract: Childhood developmental and mental disorders – including internalising and externalising symptoms – are prevalent in low- and middle-income countries (LMICs) such as South Africa. There is growing interest in the associations between polygenic risk scores (PRS), epigenetic age (EA) deviation, DNA methylation risk scores (MRS), and key neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD). However, most work has thus far been undertaken in high-income countries (HICs) with participants of European ancestry; and populations of African ancestry have been notably under-represented. The Drakenstein Child Health Study (DCHS), an ongoing South African birth cohort study, provides an opportunity to investigate the associations of PRS, EA deviation, and MRS, with childhood developmental and mental health outcomes, in an ancestrally diverse study population. This doctoral project aimed to investigate potential genetic and epigenetic associations with adverse developmental and mental outcomes in children. This aim was addressed via five objectives. First, a systematic review was undertaken to collate existing work (both in HICs and LMICs) on associations between PRS (the weighted sum of risk alleles) and developmental and mental health disorders in childhood and adolescence. A second systematic review focused on associations between EA deviation (relative to chronological age) and the outcomes of interest. Third, empirical analyses of DCHS data investigated the relationship between a PRS for ADHD, and child developmental outcomes, as well as internalising and externalising symptoms. Fourth, the relationship between gestational EA deviation at birth, and child developmental and mental health outcomes in the DCHS, was explored. Finally, the association between MRS (the weighted sum of methylation markers' beta values) at birth, and the outcomes of interest, was investigated. The systematic reviews adhered to the Preferred Reporting Items for System…
author: Moyakhe, Lihle
keywords: Childhood development, Mental disorders, South Africa
date published: 2025
date modified: 2026-07-22T22:23:04Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Psychiatry and Mental Health

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/41806