Rare Variant Discovery in Severe Early Onset Obesity driven by Electronic Health Records

Severe obesity is the fastest growing sub-category of childhood obesity despite a plateau in the overall prevalence. Youth with severe obesity have a much higher chance of being obese as an adult, and have long-term effects such as diabetes, heart disease, and even premature death. Although obesity is generally considered an effect of changes in the environment, there is a significant influence of heredity on weight gain that can vary across different races and ethnicities. Sometimes genetic differences can be valuable in creating targets for treatment such as a gene called PCSK9 that influences blood cholesterol levels. Rare genetic differences in African Americans compared to European Americans has helped develop a treatment for controlling blood cholesterol levels and prevent heart disease. It is possible that a study of genetic differences in severe obesity may explain mechanisms of weight regulation that could potentially identify areas for drug development. There is little knowledge of these genetic differences in children from minority communities although the prevalence of obesity is highest in these communities. Genetic differences are most commonly seen in the extremes of disease early in life, before significant environmental pressures. The availability of electronic health records provide an excellent opportunity to collect information about children with the condition. Hence, we aim to study rare genetic differences in a large number of children with severe early onset obesity, across different races and ethnicities, using electronic health records and their genetic information, from individuals who have agreed to participate.