Approved research

The effect of gene-by-environment interactions on obesity and cardiovascular disease risk

Lay summary

Body mass index (BMI) is a clinical risk factor for cardiovascular disease (CVD). However, the relationship is complex and depends on both lifestyle and metabolic features such as body fat distribution. In this study, we will first validate a novel genetic risk predictor for BMI, obesity and CVD through replication in UK Biobank. Next, we will test the hypothesis that lifestyle factors modify genetic risk by evaluating the effect of activity and diet related behaviors on genetic risk for obesity and CVD. Finally, we will examine the effect of body fat distribution on genetic risk for CVD. Metabolic conditions such as obesity and cardiovascular disease (CVD) are among the major causes of death worldwide. These conditions are driven by both environment and lifestyle, but also have a significant genetic component. Furthermore, it has been observed that the effect of lifestyle and environment may depend on genetics. In this study, we will investigate the relationships between environment, lifestyle and genetics to understand their combined effects on risk for obesity and CVD. Our results will lead to biological insights and help to illuminate options for the treatment and prevention of metabolic disease. First, we will apply algorithms developed at 23andMe to the UK Biobank cohort to calculate genetic risk for obesity and CAD. We will then verify that people who are predicted to be at high risk are more likely to develop the diseases. This will serve as a replication of our previous observations. Next, we will look at how likelihood of developing disease in UK Biobank individuals varies across different lifestyle and levels of genetic risk. Finally, we will examine how likelihood of disease differs between individuals with different levels of abdominal fat and how these differences relate to genetic risk. We would like to examine the full genotyped cohort.