Exploring Human Genetics Diversity to Obtain New Insights into Adipose Tissue Biology

Although there is a clear effect of genetic background in obesity development (by GWAS studies), gene variants with individually strong effects on adipose tissue growth that could be manipulated therapeutically are not extensively studied. The goal of this study is to identify genes that cause early-onset and severe obesity. Utilizing the unique population of patients of Cincinnati Children's, we are screening children with early-onset and severe obesity that are not phenotypically classic polygenic/exogenous obesity. Genome/exome sequencing is used on patients, parents and siblings to determine possible pathogenic hits. Data obtained is then verified for functionality using genetically modified mouse models and patient derived induced pluripotent stem cells (iPSC). Through this study we expect to gain a deeper understanding of basic mechanisms of adipose tissue growth in the onset of obesity in a way never used before. These insights will provide novel avenues for the development of therapeutic tools against obesity. This study is a partnership with endocrinologist Nancy A Crimmins, MD.