Approved research

Polygenic Risk Scores for Adiposity Traits in Asian Ancestry Individuals: Validation and Application to Mendelian Randomization Studies

Lay summary

Our proposal is part of a project to understand why Asian Americans have higher risk than whites for certain cardiometabolic diseases such as diabetes, despite having lower body weight and less obesity. This proposal will use information from previous genetic studies to construct risk scores for obesity and related measures of body fat and confirm that this score predicts these traits in Asians. We plan to use these scores to understand the effects of different types of fat on diabetes, heart disease, and kidney disease. This proposal will contribute to a project which aims to identify opportunities to prevent diabetes, coronary heart disease, kidney disease, and dementia. Our primary focus is on explaining the paradoxical patterns of these conditions in Asian Americans compared to whites in the United States. In the larger project, we will consider both genetic and socioenvironmental risk factors, but in the UK Biobank we in particular wish to validate our genetic risk scores and conduct parallel Mendelian Randomization analyses. Our findings will show how different types of adiposity influence chronic disabling diseases, and therefore identify opportunities to prevent these conditions. Using data on the genetic profile of each person identified as Asian or white in the UK Biobank, we will construct genetic risk scores for body mass index (BMI) and other adiposity phenotypes (waist circumference, subcutaneous adipose tissue) and evaluate whether each of these genetic risk scores predicts relevant phenotypes in Asians. After constructing genetic risk scores, we will evaluate associations with diabetes, coronary heart disease, and kidney disease in Asians. We would like to use all participants identified as white or Asian. Our primary interest is in Asians, but we will use evidence from whites to strengthen analyses in Asians.