Genetics, blood pressure and major causes of death in a large Hispanic population (MRC-PHRU)
Genome-wide association studies have identified several hundred common and low frequency genetic variants associated with blood pressure, but the vast majority of these have been done in populations of European ancestry (which covers only a subset of human evolution). Additional large genetic studies of non-European populations are needed to fully study the influence of genetics on blood pressure.
The Mexico City Prospective Study (MCPS) includes 150,000 adults who were recruited during 1998-2004 from two districts of Mexico City, with extensive data collected from questionnaire and physical measurements (including blood pressure), and follow-up through linkage to death registries. To date, more than 20,000 have died, with the leading causes being cardiac disease, kidney disease and other vascular/metabolic causes. All participants provided a blood sample at recruitment and, by the time the DPhil starts, genome-wide genotyping data will exist for each participant.
The specific DPhil project will be subject to further discussion and personal interest, but may include the following areas of work:
- Conducting a genome-wide association study of blood pressure, assessing overlap with known BP loci from other populations, and creating new genetic risk scores for blood pressure;
- Using Mendelian randomisation to assess the causal relevance of blood pressure to death from particular causes (especially cardiac and kidney disease), and how those effects vary depending on other characteristics.
- Fine-mapping studies and trans-ethnic meta-analysis.
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 fieldwork, industry placement 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.