This multidisciplinary project will integrate expertise across cleft, genetic epidemiology, mental health, and epidemiology. The candidate will have the opportunity to develop into one of few experts globally with in-depth understanding across these fields. Training will involve a mini-MD in the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff: The student will spend 6 months with the Cardiff team and take part in assessments visits in the homes of families with a child with a genetic syndrome, learn to conduct neurocognitive and psychiatric assessments, and take part in consensus meetings to evaluate psychiatric diagnoses.
Cleft of the lip and/or palate is a common birth defect and occurs at a rate of one in 650 live births in the UK. Being born with cleft places a significant burden on children, their families and the health system as they require surgery (multiple times depending on cleft type), and other interventions to improve appearance, speech, hearing and dentition. They are also at increased risk of mental health and neurodevelopmental problems (Berman et al 2022).
The aetiology of both cleft and of mental health outcomes is complex, with common risk alleles (Cleynen et al 2021, Howe et al 2018) of individually small effects as well as rare genetic mutations of large effect and environmental factors playing roles. One group of rare mutations of large effect are Copy Number Variants (CNVs), referring to deletion or duplication of a part of the genome leading to differences between individuals in the number of copies of genes within the affected region. A number of CNVs are known to increase risk of neurodevelopmental disorders (ND-CNVs), such as ADHD and autism, as well as mental health disorders but the presence and the impact of ND-CNVs have not been studied in cleft (Chawner et al 2019).
The PhD project will provide the first detailed description of neurodevelopmental and mental health outcomes in children with cleft and examine the contributions of genetic and environmental factors. We will use two unique genetically informative clinical cohorts of children; the University of Bristol Cleft Collective (www.bristol.ac.uk/dental/cleft-collective/) and the Cardiff University longitudinal ExperiencCes of people with copy number variants (ECHO) study. Control samples will consist of the Avon Longitudinal Study of Parents and Children (ALPSAC) and the Millennium cohort which are deeply-phenotyped cohorts of typically developing children.
The aims of the study are:
- To improve understanding of risk of neurodevelopmental and mental health problems in children born with cleft.
- To improve understanding of the causes of neurodevelopmental and mental health problems in children born with cleft. This will be achieved by determining in children born with cleft the contribution of: a) composite genetic (polygenic) risk scores for neurodevelopmental and psychiatric disorders and b) rare genetic mutations.
- To improve understanding of non-genetic factors, the project will also examine contributions of early developmental problems, family socio-economic status, family relationship quality, and traumatic experiences to risk of childhood psychiatric disorders in children born with cleft. The student will be able to take part in consultations with the Cleft Collective Patient and Public Involvement (PPI) group and steer the project towards non-genetic factors that they have identified as important for families affected by cleft.
How to apply
This project is part of the GW4 BioMed2 MRC DTP projects.
Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’. If successful, you will also need to make an application for an 'offer to study' to your chosen institution.
Please complete the online application form linked from our website by 5.00pm on Wednesday, 1st November 2023. If you are shortlisted for interview, you will be notified from Tuesday 19th December 2023. Interviews will be held virtually on 24th and 25th January 2024. Studentships will start on 1st October 2024.
For enquiries regarding the application procedures please contact [Email Address Removed]
Interested candidates should contact Evie Stergiakouli [Email Address Removed] for informal discussions about the project.