Investigating causal relationships between chronic pain and major depression using UK general population datasets with whole-genome genotyping

MRC DTP in Precision Medicine

Up to 26 fully funded studentship positions are available across the University of Glasgow and Edinburgh. Our next intake will be for PhD projects commencing September 2017.

The Precision Medicine Doctoral Training Programme (DTP) offers PhD with Integrated Study studentships funded by the Medical Research Council (MRC), The University of Edinburgh and the University of Glasgow. Hosted by the University of Edinburgh in collaboration with the University of Glasgow and the Karolinska Institute, this prestigious programme provides PhD research training alongside taught courses over four years of study and welcomed its first cohort of students in September 2016.

This new Doctoral Training Programme focuses on training PhD students in key MRC skills priorities in quantitative skills (mathematics, statistics, computation, and developing digital excellence) as applied to variety of data sources (from ‘omics’ to health records), and interdisciplinary skills including imaging and stratified medicine.

Supervisors
Dr Barbara Nicholl – [Email Address Removed]
Prof Andrew McIntosh – [Email Address Removed]
Prof Daniel Smith - [Email Address Removed]
Dr Mark Bailey - [Email Address Removed]

Abstract
The overall aim of this PhD project is to clarify the extent to which the genetic correlation between depression and chronic pain is due to misclassification, mediation or pleiotropy, to assess the directional pathways of any association and to utilize this knowledge to improve the classification and stratification of both disorders. To do this we will use two large cohort studies, UK Biobank and Generation Scotland.

Chronic pain and depression are highly prevalent and often comorbid conditions. They are currently the two most common causes of disability globally in terms of days lived with disability. Whilst an observed genetic correlation between chronic pain and depression is important, it remains unclear whether this is due to pleiotropy (individual genes conferring risk to both disorders independently), heterogeneity or mediation. Recent cutting-edge analysis methods are available to distinguish between pleiotropy, heterogeneity and mediation, e.g., http://software.broadinstitute.org/mpg/buhmbox/). Further refinements to these packages are also able to test for directional relationships using techniques such as Mendelian Randomization with adjustment for pleiotropy. Understanding these relationships will improve the classification of these conditions, allow us to stratify chronic pain patients according to depression-related processes and lead to new and/or more effective treatments.