Mexico City Prospective Study: polygenic risk scores for vascular-metabolic mortality risk in Mexico (MRC-PHRU)
Polygenic risk scores (PRSs) can potentially enhance risk stratification and prevention for chronic diseases. Studies from populations of European ancestry have demonstrated that genetic instruments can improve the classification of cardiovascular (CVD) risk when added to conventional risk factors, and hence provide opportunities for more effective disease prevention strategies. However, the value of such scores for predicting CVD risk in non-European populations is uncertain.
The Mexico City Prospective Study (MCPS) is a blood-based prospective study of 150,000 adults who were recruited between 1998 and 2004 and have been followed for cause-specific mortality ever since. Questionnaire data (including lifestyle characteristics, prior diseases and medication use), physical measurements and glycosylated haemoglobin was recorded at baseline, and genome-wide genotyping and whole exome sequence data exists for all participants. Baseline NMR metabolomics data (largely characterising blood lipid particles) also exists in a subset of 40,000 participants.
The specific DPhil project will be subject to further discussion and personal interest, but the main aims are to:
- Develop and evaluate genetic-risk instruments for vascular-metabolic risk in the MCPS population;
- Estimate differences in risk-stratification by different genetic and conventional risk scores, and model the potential implications for vascular-metabolic disease prevention and treatment in a general population setting.
RESEARCH EXPERIENCE, RESEARCH 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.
FIELD WORK, SECONDMENTS, 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 and genetic 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.