Taking a Closer Look at Type 2 Diabetes (T2D) through PheWAS

Tuesday, April 11, 2017 -
4:00pm to 5:00pm
Biotechnology Center Auditorium, 425 Henry Mall

Speaker Name: 

Jamie Fox, PhD

Speaker Institution: 

CIBM postdoctoral fellow, Marshfield Center Research Institute




The worldwide incidence of type 2 diabetes has rapidly increased over the last several decades. This increase has far-reaching ramifications including burdensome health care costs and decreased quality of life. Through genome-wide association studies (GWASs), many genetic variants have been associated with T2D onset, but these studies have been unable to identify distinct casual variants. Using phenome-wide associations studies (PheWASs), we have associated several T2D variants with disease phenotypes using electron health records of patients genotyped in the Marshfield Clinic Personalized Medicine Research Project (PMRP). Our top PheWAS hits include expected phenotypic associations: TCF7L2 (rs34872471) with T2D, and FTO(rs8050136) with obesity, as well as unexpected associations: APOC1(rs4420638) with Alzheimer’s Disease/dementia, and HMGA2(rs343092) with presbyopia/myopia. Using PheWAS as a platform, we can further explore genetic variants that lead to disease phenotypes through statistical analyses including: gene-based association testing, measurement of pleiotropy, and pathway analysis. In addition, we have used phenotype information gained from PheWASs to develop targeted cell-based assays to functionally validate genetic variants within the gene SLC5A2, an important target for T2D therapeutics. These studies have applications in pharmacogenetics, drug repurposing, and contribute to advancing the newest clinical efforts in precision medicine.