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Transferability of genetic risk scores for complex human diseases across diverse population groups


Project Description

Genome-wide association studies (GWAS) have been extremely successful in identifying DNA variants that are associated with a wide range of complex human traits and common diseases. One potential route to the clinical translation of GWAS is to use these DNA variants to build genetic risk scores (GRS) to predict future disease occurrence in individuals that are currently healthy. However, to date, most GWAS have been undertaken in populations of European ancestry, and there has been considerable debate as to the transferability of GRS to predict disease in other ethnic groups.

This project will use GWAS of a range of complex human traits and common diseases (including type 2 diabetes, kidney function and rheumatoid arthritis) across diverse populations that are available to the supervisory team to perform a detailed evaluation of the predictive power of GRS across different ethnic groups. The project will compare GRS built in European ancestry GWAS with those built by combining GWAS across populations through trans-ethnic meta-analysis. The findings of these transferability analyses will be supported through simulations, and depending on the background of the student, could include a component of developing novel statistical approaches to build GRS from multi-ethnic GWAS.

Training/techniques to be provided:
The student will be integrated into an interdisciplinary and active research group at the Centre for Genetics and Genomics Versus Arthritis (CfGG). The student will attend regular centre-wide lab meetings and journal clubs, covering genetics, functional genomics, and bioinformatics. The student will also present at CfGG seminars to gain experience in formal presentations. Training in quantitative skills (statistics, data analytics and bioinformatics) and “big-data” handling applied to genetics will be provided by the supervisory team. Additional training and skills development opportunities will be provided through attendance and presentation of results at national and international conferences, such as the American Society of Human Genetics. The student will attend GWAS-specific training courses, including the Wellcome Advanced Course on “Design and Analysis of Genetic Association Studies”.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in genetics or statistics. Candidates with an interest in applying genetics to understand and improve human health are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 1 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Martin AR, et al. (2019). Clinical use of current polygenic risk scores may exacerbate health disparities. Nature 51: 584-91.

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