Heterogeneity of heritable risk in coronary disease
Genome-wide association studies (GWAS) have identified scores of loci that influence susceptibility to coronary disease. This progress has been largely driven by international meta-analysis collaborations, pooling data from studies commissioned independently with a variety of sampling protocols. The genetic signals typically show differences between studies that may reflect underlying differences in risk factor profiles, clinical phenotypes and ancestry.
We propose to examine these potential sources of heterogeneity in the UK Biobank, which provides detailed longitudinal clinical data to accompany high-resolution genetic data in a prospective study of 500,000 British participants.
This genetic epidemiology project involves computational, bioinformatics and statistical genetics research methodologies. Students will acquire fluency in programming in at least one high-level statistical analysis package (e.g. R, Stata). There will be opportunities to develop informatics skills (e.g. perl programming) as well as generic bioinformatics skills. The project is based in the Wellcome Trust Centre for Human Genetics, which has excellent computational core facilities, infrastructure and expertise and a thriving community of bioinformaticians and statistical geneticists who enjoy focussed seminars and workshops. We also enjoy close collaborations with genetic epidemiologists in the Nuffield Department of Population Health, with complementary expertise in a broad range of epidemiological and public health science methodologies.
As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.
|1||Magosi LE et al. Identifying systematic heterogeneity patterns in genetic association meta-analysis studies. PLoS Genet. 2017 13(5):e1006755.|
|2||Nelson CP et al. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet. 2017 doi: 10.1038/ng.3913.|
CARDIoGRAMplusC4D Consortium. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015 47(10):1121-30.