Genetic causes of major non-communicable diseases in a large Hispanic population (MRC-PHRU)
Genome-wide association studies have identified thousands of common and low frequency genetic variants associated with major non-communicable diseases (eg, cardiovascular disease and diabetes) as well as their major risk factors (eg, adiposity, blood pressure, blood lipids). However, the vast majority of these studies have been done in populations of European ancestry, which covers only a subset of human evolution. Additional large studies of non-European populations are needed to fully study the influence of genetics on disease.
The Mexico City Prospective Study (MCPS) includes 150,000 adults who were recruited during 1998-2004, with extensive data collected from questionnaire and physical measurements, as well as from a blood sample taken at recruitment. Follow-up is through linkage to death registries, with more than 20,000 deaths recorded to date (many due to cardiovascular and other metabolic diseases). By the time the DPhil starts, genome-wide genotyping data and exome sequence data will exist for all participants, while NMR metabolomics data (largely characterising blood lipid particles) will exist for at least 50,000 participants.
The specific DPhil project will be subject to further discussion and personal interest, but could include the following areas of work:
- Conducting genome and exome-wide association studies of major non-communicable diseases (and/or their established major risk factors) after accounting for the admixed nature of this population;
- Assessing overlap of association results with known loci from other populations, and integrating results with expression, pathway or other external datasets to elucidate the functional basis for the associations;
- Creating genetic risk scores and conducting Mendelian randomisation studies to assess the causal relevance of known or novel disease risk factors to particular diseases.
Research experience, methods and training
This project will involve detailed analysis and interpretation of existing MCPS data. The student will work within a multi-disciplinary team and will gain research experience in literature review, epidemiological and statistical methodology (including genetic epidemiology techniques), programming and data analysis. Regular research meetings and workshops will be held in which the candidate will be expected to attend and to present research findings.
Planned field work, industry placements and training
The project will provide a range of training opportunities in statistical analysis and interpretation and statistical programming. By the end of the DPhil, it is expected that you will be competent to plan, undertake and interpret statistical analysis of large-scale epidemiological data, and to report your findings. The project will be based in the MRC Population Health Research Unit, Nuffield Department of Population Health, which has excellent facilities and a world-class community of statistical and clinical scientists.
Candidates should have a strong background in a mathematical or biomedical discipline and postgraduate training in epidemiology, statistics or public health. The project will involve large-scale data and statistical analyses. Candidates should therefore have an interest and aptitude in extending these skills as well as a strong interest in non-communicable disease epidemiology.