Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Defining Networks of Interacting Genetic Variants that Contribute to Type 1 Diabetes, Type 2 Diabetes and Diabetes Complications (#68)

Grant Morahan 1 , Munish Mehta 1 , Ramesh Ram 1 , Timothy ME Davis 2 , Wendy A Davis 2
  1. Harry Perkins Institute of Medical Research, Nedland, WA, Australia
  2. School of Medicine and Pharmacology, University of Western Australia, Perth

Recent advances in genetic research have led to the identification of over sixty loci that contribute to the susceptibility of developing Type 1 diabetes (T1D) and even more for type 2 diabetes (T2D). The plethora of genetic risk variants that has been identified may be overwhelming for clinicians faced with lists of gene names and symbols that have little bearing on management; it also provides a challenge for researchers to identify the mechanism by which these variants contribute to disease, and to place the genetics of diabetes in a more amenable clinical context We examined the genetic data from 3,348 T1D subjects and produced evidence that defined six disease subtypes based on genotypes at HLA and 19 non-HLA loci. Validation demonstrated that affected siblings were highly likely to share the same T1D subtype, consistent with a genetic basis for each subtype. The T1D subtypes differed significantly in all clinical features examined, including age at diagnosis, autoantibody status and presence of other autoimmune diseases. We applied our method to define subtypes of both T2D and diabetic nephropathy. These subtypes also differed in important clinical features. Definition of genetic subtypes may allow better characterization, prevention and clinical management of people with diabetes.