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Investigating hypomania to get closer to the aetiology of bipolar disorder: examination of genes, the environment and their interplay

  • Full or part time
  • Application Deadline
    Thursday, January 02, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Applications are invited from graduates with a BSc (First or Upper Second) or MSc (Distinction), or equivalent, to work within the Wolfson Institute of Preventive Medicine. This 3 year studentship will commence in Spring 2020 and will be based at the Charterhouse Square Campus. This is an exciting opportunity for a graduate from disciplines related to epidemiology, statistics, and behavioural sciences.

Project description

Background: Bipolar disorder is a serious psychiatric illness characterized by episodes of mania or hypomania (symptoms include, elation and grandiosity) and depression. The causes of bipolar disorder are largely unknown, although there is consensus that it is likely to be the result of complex interactions between genetic and environmental factors. One approach to investigating the aetiology of bipolar disorder is by studying hypomanic symptoms in a similar way that the study of depressive symptoms are used to explore the aetiology of major depression. To date there is limited available research on the origins of hypomania and will be the focus of this project. Specifically this PhD will focus on whether hypomanic symptoms reported by people from the general population (that don’t meet the clinical diagnosis of bipolar disorder) are associated known genetic and environmental factors linked to bipolar disorder. In addition, the genetic architecture of hypomania will be examined along with the effects of possible gene-environment interactions and correlations. Data from UKbiobank will be used to address the aims of this project.

Research aims:
The PhD project will address 3 main aims:
1) To examine the correlation between genetic risk for BD and hypomanic symptoms reported in a general population sample.
2) To explore the role of positive and negative life stressors on hypomania
3) To conduct the largest ever genome-wide association study of hypomanic symptoms in UKbiobank
4) To investigate the interplay between genetic factors and life stress on hypomania

Method: All four aims of this PhD will be addressed by conducting analysis of existing data from the UK Biobank (16). Sample and measures: The UKBiobank includes over 500,000 participants who have completed self-report measures of hypomanic symptoms, adverse experiences (eg. stressful events) and positive experiences (eg. supportive interpersonal relationships). Genome-wide genetic data is available on all participants. Analyses: A genome-wide association study will be conducted on hypomanic symptoms in UKbiobank (Aim 3). This will allow us to investigate the relationship between genetic risk for BD and hypomanic symptoms (Aim 1) and environmental risk and protective factors (Aim 2) using LD score regression and polygenic scoring using the method outlined by Purcell et al (17). The relationship between risk and protective environmental factors and depressive and hypomanic symptoms will be tested using linear regression models. The extent to which genetic risk for BD moderates the effects of these environmental factors will be tested by including polygenic score by environment interactions in the above models (Aim 4).

Timetable:
Year 1: Attend training course on complex genetic analyses, complete analyses and write up for aim 1 and 2 and draft paper for publication. Attend conference to present findings.
Year 2: Complete analyses and write up for aim 3 and draft paper for publication. Attend international conference to present findings from aim 3.
Year 3: Complete analyses and write up for aim 4 and draft paper for publication. Organise symposia at an international conference and present findings, complete thesis writeup and submit.

Training: Wellcome Genome Campus’ ‘Genetic Analysis of Mendelian and Complex Disorders’ training course, which will equip the student with the statistical skills needed to conduct the genome wide association study and downstream analyses.

About the candidate: This PhD would be suitable for a candidate with a background in psychology, psychiatry and/or genetics with an interest in mental health particularly bipolar disorder. The successful candidate will be keen to undertake interdisciplinary work using advanced statistics.

Informal enquiries can be made to via email: Dr Georgina Hosang

How to apply
Your application should consist of a CV and contact details of two academic referees. You must also include a personal statement (1,000 words maximum) describing your suitability for the selected project including how your research experience and interests relate to the project.

Please submit your application to: Patrick Mullan ().


Funding Notes

This 3 year PhD studentship is funded by the Wolfson Institute of Preventive Medicine and comes with a tax-free stipend of £21,000. It is open to UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the EU prior to the start of the studentship. University tuition fees (at UK/EU levels) will be met by the Institute.

References

Hosang, GM, Cardno, A, et al (2017). Characterization and structure of hypomania in a British nonclinical adolescent sample. Journal of Affective Disorders, 207, 228-235.

Hosang, GM, Uher, R, et al. (2012). The role of loss and danger events in symptom exacerbation in bipolar disorder. Journal of Psychiatric Research, 46 (12): 1584-1589.

Assary E, Vincent JP, Keers R, Pluess M. (2017) Gene-environment interaction and psychiatric disorders: Review and future directions. Seminars in Cell and Developmemental Biolology, 77, 133-143

Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, et al. (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460(7256):748–52.

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