Blood biomarkers, genetic factors and risk of stroke subtypes: the China Kadoorie Biobank study
Project Reference: NDPH/MT16/045
Stroke is a leading cause of mortality and disability globally. China has particularly high stroke rates, despite the population being relatively lean. Within China, large unexplained variations in stroke rates exist between different regions, suggesting important causes remain to be discovered. Many hypotheses have emerged about the relevance of particular blood-related factors (including genetic variants) to stroke risk, but most have not yet been tested in large well-designed epidemiological studies. Even for certain known biomarkers (eg, LDL-C, HDL-C), uncertainty remains about their causal associations with stroke subtypes. Moreover, there is limited evidence about the relevance of emerging biomarkers (eg, metabolomics, inflammation) and genetic factors to stroke. The China Kadoorie Biobank study is a blood-based prospective study of 0.5M people recruited during 2004-08. To date, ~35,000 confirmed incident cases of stroke, including >5,000 haemorrhagic strokes, had been recorded. This, together with genome-wide SNP, metabolomic, proteomic and blood biochemistry data that are being generated will allow for reliable assessment of causal relevance of blood biomarkers and genetic factors for stroke.
Research Experience, Research Methods and TraininG
The project will involve experience and training in literature review, study design and planning, novel analytic methods, and statistical analysis, interpretation and reporting of large-scale multi-dimensional epidemiological data. The specific line of investigation will be subject to further discussion and personal interest, and may include certain aspects of the following:
- Investigate the relationships between several known and emerging biomarkers (eg, lipid, lipid fractions, lipoproteins, metabolomics) and stroke subtypes;
- Assess the causal role of blood biomarkers in stroke risk, using Mendelian Randomisation approach;
- Explore interactions between blood biomarkers and other lifestyle factors (diet, physical activity, smoking, alcohol) and between genes and lifestyle factors on stroke risk;
- Use genetic, biochemistry and other multi-omic data to explore biological pathways and mechanisms linking particular biomarkers with stroke subtypes;
Develop predictive models based on the exposure information related to lifestyle, physical characteristics and blood biomarkers.
Field Work, Secondments, Industry Placements and Training
The DPhil will be based at CTSU, and there may be opportunities for involvement in laboratory (eg, NMR-based metabolomics), or field work in China. The candidate will be expected to publish 3-4 peer-reviewed papers by the end of DPhil study.
The candidate should have a 2.1 or higher degree in medicine, medical sciences or a related discipline, and an MSc in epidemiology/statistics/genetics/population health would be an advantage.