Trans-ethnic genetics and genomics of major diseases (MRC PHRU)
Genetic association studies have been successful in identifying genes and pathways that play roles in a wide range of diseases and disease risk factors, but the majority of such studies have used individuals predominantly of European ancestry. It is becoming increasingly important to understand the genetic architecture of disease and disease traits in ancestries other than Europeans, not only to understand the difference between populations, but also to exploit the contrasting patterns of association for “fine mapping” of the “causal variants” that are responsible for the observed association.
The China Kadoorie Biobank (CKB) and UK Biobank studies, each of over 0.5 million adults, include extensive questionnaire-based health and lifestyle data; detailed physical measurements at baseline; a wide range of biochemical and imaging measurements; and prospective follow-up for incident disease events. Genome-wide genotyping is available for the full UKB cohort and for 102,000 CKB participants, with whole genome sequencing of both biobanks underway. Together, these provide unprecedented opportunities for conducting large-scale genetic association studies of disease and disease risk factors, and for comparing the genetic architecture of disease in Europeans and East Asians.
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
A wide range of genetics and genomics projects are available. The precise project will depend on the student’s interests and aptitude, but will likely include: genome-wide association analysis of relevant traits; experience in all stages of data QC and association analysis; transethnic meta-analysis of association data from CKB and UKB; potential for involvement in international collaborations and/or consortia.
Examples of possible project areas include:
• Stroke and stroke subtypes
• Reproductive traits
• Educational attainment
• Infection and immunity
There will be in-house training in epidemiology and in statistical and computational genetics, and attendance at relevant courses including the Wellcome Trust course “Genetic Analysis of Population-based Association Studies”. By the end of the DPhil, the student will be able to plan, undertake and interpret analyses of large-scale genetic data, and to report research findings, including publications as the lead author in peer-reviewed journals and presentation at national/international conferences.
FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING
The project will be based within the CKB research group, part of the Nuffield Department of Population Health and based in the Big Data Institute. There are excellent facilities and a world-class community of genomics and population health scientists. There will be opportunities to collaborate across scientific disciplines and potential for involvement in international collaborations and/or consortia, depending on the direction of the project.
The candidate should have a strong background in genetics, statistics and/or computational biology. The project will involve large-scale data and statistical analyses and, therefore, requires some aptitude for data handling and programming. Prior experience is not essential, as training will be provided.