The genetics underlying imaging phenotypes and correlated physiological measures

Additional Supervisor: Claire Tochel, UK Biobank Data Analyst

Background

Imaging techniques are widely used for early detection and diagnosis of disease. Although widely adopted in clinical practice, it is only partially understood how structural information in medical images relates to physiological function, which may amenable for treatment. Furthermore, our understanding of how imaging phenotypes are determined by genetics and to what degree the genetic control of disease and the imaging phenotypes is shared is very limited. Identifying which imaging phenotypes have genetic correlations (i.e. a genetic shared component) with the disease of interest would inform of shared control pathways and to match disease-subtypes and imaging phenotypes to different biological pathways.

Furthermore, computational modelling approaches can be used to convert structural images into physiologically relevant traits. During this project we will develop both structural measurements and modelling-based estimates of blood flow (i.e. haemodynamics) in the eye from retinal imagines in UK Biobank, a large prospective epidemiological study of 500,000 individuals. Our goal is to identify genes influencing the structural and haemodynamic measurements and dissect their genetic and environmental variation.

Aims

To develop structural and haemodynamic measurements in retinal scans of circa 100,000 UK Biobank participants leading to robust biomarkers.
To estimate heritability (i.e. the importance of genetics) of these biomarkers.
To perform a genome-wide and environmental-wide association studies of these traits.
To identify which of the developed biomarkers have the largest shared genetic components in particular in the context of diabetic retinopathy and other small vessel diseases.
Training Outcomes

The successful candidate will work in at the interface of computational Biology and physiology to develop the structural measurements and models of blood flow from retinal images under the supervision of Miguel Bernabeu. Once the phenotypes are generated the person will work on the field of genetics and genomics under the supervision of Albert Tenesa. A background on a mathematically related discipline and programming skills are essential, hence the ideal candidate would be someone with such background wishing a career in biology or medicine related fields.

The expected outcomes of the training programme are:

Proficient programming skills
Advance mathematical and statistical models
Quantitative genetics and genomics
In depth understanding of the physiology of the eye
Handing of large volume of data (Big data), both in the handling of images and the genetic data

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location:

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you are encouraged to contact the primary supervisor prior to making your application. Additional information on the application process if available from the link above.

For more information about Precision Medicine visit:

http://www.ed.ac.uk/usher/precision-medicine