Comparison of Genetic Risk Factors Between Two Type II Diabetes Subtypes

Abstract

Type 2 Diabetes (T2D) is an extremely heterogeneous disease, and the heritability of T2D is not fully accounted for. This study seeks to determine T2D subtypes based on clinical features before T2D diagnosis, and to test whether genetic risk factors differ between the subtypes. A sample of 13,459 White, GWAS study participants was obtained from FRAM, MESA, and ARIC. This sample consisted of 832 cases (individuals who developed T2D during follow-up) and 12,066 controls (did not develop T2D). K-means clustering was used to cluster individuals in the cases dataset based on metabolic and anthropometric characteristics. Cox proportional hazards models were used to test whether T2D genetic risk factors differed between the groups. The clustering analysis resulted in two clusters with cluster one consisting of a higher percentage of women with higher WHR, lower HDL, and higher FI as compared to cluster two. There were no statistically significant differences between the genetic risk factors of the two clusters. The most significant differences in genetic risk factors were associated with adiposity, suggesting some interaction between adiposity genes and the characteristic phenotypes of each cluster on T2D development. Further research is needed to replicate subtypes and to find significant genetic associations.