Cardiff University PhD Studentship in Medicine
The research will take place in the MRC Centre for Neuropsychiatric Genetics and Genomics (MRC CNGG) which is based in the new state-of-the-art Hadyn Ellis Building. The MRC CNGG has a vibrant research culture and excellent facilities for the pursuit of this research. The student will have access to support and expertise from world-class researchers, specialist local training and wider training offered by the Graduate College. The student will be able to attend selected modules in Statistics, Genetic Epidemiology, and/or Computing (depending on the student’s needs) on the MSc course in Biostatistics and Bioinformatics, which is run between the Schools of Biosciences, Medicine and Computer Science department at Cardiff University.
Project title: Heterogeneity in depression: examining hypothesis-driven subtypes in longitudinal genetically informed cohorts
Depression is common and is one of the leading causes of disability worldwide. Despite its societal importance, relatively little is known about what causes depression. However, it is recognised that multiple causal factors are involved with both environmental and genetic factors contributing. There is considerable heterogeneity both in the types of symptoms exhibited by depressed individuals and in the long-term trajectory of symptoms. It is possible that there are sub-types of depression with different causal factors. For instance, the relative contribution of genetic influences appears to be greater for more severe depressive symptoms (Riglin et al., 2015), lowest for childhood onset depressive symptoms (Rice et al., 2002) and vary according to whether depression co-occurs with other difficulties such as antisocial behaviour (Riglin et al., 2015). This proposal aims to synthesise findings from genetic epidemiology and developmental psychopathology to generate and test hypotheses about subtypes of depression. This information will help to further understanding about the causes of depression and may ultimately help to improve services for depressed people and their families.
Findings from family, twin and longitudinal studies of depression suggest that particular factors may be important to consider for identifying depression sub-types. 1) Several studies suggest that adolescent onset depression that recurs in adult life may indicate a subtype of depression which has a particularly malignant long-term trajectory which is more common in those with a family history of depression (Rice, 2010). 2) Depression that co-occurs with antisocial behaviour problems may differ from depression that does not co-occur with these problems and ‘co-occurring depression’ may be common in children (Riglin et al., 2015).
The aim of this project is to investigate whether there are subtypes of depression with differing genetic and environmental risk factor profiles and associated phenotypic and functional outcomes. For example, in relation to the first hypothesis, adolescent onset depression that recurs in adult life would be expected to show moderate to high heritability, to be associated with family history of depression, and genetic risk burden (polygenic risk score) for depression as well as with depression-related outcomes in adult life such as symptom trajectory and service use. In order to address the primary research question, longitudinal genetically informed data with rich phenotypic information and information on environmental risk and protective factors is required. The project will utilise several unique datasets well suited for addressing the research question:
1. Cardiff Study of All Wales and North England Twins (CaStANET): a study of 1500 adolescent twin pairs.
2. The Early Prediction of Adolescent Depression (EPAD) study: a longitudinal study of 335 offspring of depressed parents.
3. 1958 National Child Development Study (NCDS): a longitudinal birth cohort of 17000 individuals.
4. The Avon Longitudinal Study of Parents and Children (ALSPAC): a longitudinal birth cohort of 14000 mothers and children.
5. The Psychiatric Genomics Consortium (PGC): genome-wide genotype and summary genome-wide association and genetic risk data from approximately 17000 affected and 26000 individuals unaffected by major depressive disorder.
The MRC CNGG provides an ideal environment in which to address this research question due to the exceptional local computational infrastructure, readily available training opportunities and the centre’s internationally recognised research excellence in the area of psychiatric genetics. This project is supported by supervisors with expertise in depression, genetic epidemiology, statistics and genomics meaning that the student will have access to a broad array of relevant expertise.
The most appropriate of the available data sets will be selected to test key hypotheses. Longitudinal data sets will be analysed using appropriate techniques (e.g. latent profile analysis, latent class growth curve analysis) to assess whether there are sub-groups of individuals with differing trajectories of depressive symptomatology. Heritability of profiles can be tested in the twin sample and in studies containing genome-wide genotype data. Polygenic risk profiles for depression will be derived, from best-available data (e.g. PGC) in individuals with genome-wide genotype data. Associations between trajectory grouping with polygenic risk scores, social risk factors and clinical and functional outcome will be examined. Replication will be sought in the most appropriate available data set. Training in all relevant methods will be provided. This project would suit a student with a psychology, statistical or bioinformatics background.
References
Riglin, L., Thapar, A., Shelton, K.H., Langley, K., Frederickson, N., Rice, F. (2015). Profiling depression in childhood and adolescence: the role of conduct problems. Journal of Child Psychology and Psychiatry. doi: 10.1111/jcpp.12465.
Rice, F., Harold, G.T, Thapar, A. (2002). Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence. Journal of Child Psychology and Psychiatry, 43, 1039-1051.
Rice , F. (2010). Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research. Genome Medicine, 2, 68.
Supervisors: Dr Frances Rice , Dr Richard Anney & Professor Anita Thapar
Supervision will be provided by an inter-disciplinary team of researchers with expertise in developmental psychopathology, mood disorders, genetic epidemiology and bioinformatics. Dr Frances Rice has substantial experience in running studies of depression and developmental psychopathology. Dr Frances Rice will oversee all of the developmental aspects of the project. Dr Richard Anney has substantial experience in the study of genetic risk, specifically in relation to this project the study of psychiatric genomics including genome-wide association analyses and polygenic risk profiling. Professor Anita Thapar is an international leader in the field of child psychiatry and will provide advice on child psychiatry and phenotype aspects of the project.
Funding
This studentship consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,057 p.a. for 2015/16, updated each year).
One studentship is available.
Additional funding of the value £2550 for conference attendance, fieldwork allowance and travel allowance is available.
Eligibility
Academic criteria: Minimum degree classification 2:i in a relevant subject area (e.g. psychology, genetics, statistics). Experience of working in a research environment is desirable. Experience of statistical analyses and working with large data sets is desirable.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students without further restrictions.
How to Apply
In the first instance, you should submit a CV & Covering Letter to Dr Frances Rice. The successful candidate will then be invited to submit a standard application for Postgraduate Study via the Online Application Service.
The deadline for applications is 15 July 2016.
Cardiff University reserves the right to close applications early should sufficient applications be received.
Further Information
For further information please contact Dr Frances Rice either on e-mail ricef2@cardiff.ac.uk or via Telephone on +44 (0)29 2068 8384
This opportunity has expired. It was originally published here:
http://courses.cardiff.ac.uk/funding/R2740.html