Novel Gene-Diet Interactions and Determinants of Health in High-Risk Minority Groups

Minority ethnic groups can be up to 5-fold greater risk of cardiometabolic disease and cancers, compared to the general population. Studies demonstrate that ethnic-specific risks persist throughout life and that part of the risk stems from inherent metabolic differences between ethnic groups.

Previous evidence that (i) Asians metabolise polyunsaturated fatty acids more efficiently than white Europeans and (ii) the microbiome of South Asian infants is significantly different from white Europeans infants are just two examples of this. This suggests that the same diet can impart different effects between ethnic groups. This agrees with recent work demonstrating that adherence to plant-based diets during pregnancy associated with different infant birthweight trajectories in white Europeans and South Asians. In short, the evidence suggests that ethnic-specific metabolic adaptations are accountable for the heightened level of cardiometabolic risk observed in minority ethnic groups. Metabolite-genome wide (mGWAS) approaches bridge the gap between genomics and metabolomics, by allowing researchers to quantify the metabolic effect of a genetic variant. By identifying genetic variants that influence metabolism we can then investigate where there are genetically-driven metabolic differences between different ethnicities, without having to worry so much about the confounding factors (e.g., lifestyle).

For this proposal, mGWAS will be supplemented with molecular and nutritional epidemiological methods to identify:

(i) ethnic-specific gene-metabolite associations with a causative effect (using Mendelian randomisation) and

(ii) ethnically-appropriate foods than offer a preventative therapy. As part of this work the student will work with data collected as part of the Born in Bradford cohort to: (i) construct ethnic-specific polygenic risk scores of glucose sensitivity;

(ii) identify ethnic-specific metabolites that associate with glucose sensitivity; and

(iii) identify genetic characteristics that underlie the ethnic-specific in differences in metabolism and glucose sensitivity. T

his research will identify inherent ethnic-specific determinants of dysglycaemia in a high-risk minority group population and provide future direction for interventions that aim to mitigate this risk. Furthermore, this studentship will demonstrate the importance of recognising population-specific determinants and further the push for population-specific interventions. In short, this work will help inform future studies and interventions seeking to reduce healthcare inequalities in the UK and globally.