The genetic risk for type 1 diabetes has been studied for over half a century, with the strong genetic associations of type 1 diabetes forming critical evidence for the role of the immune system in pathogenesis. In this review, we discuss some of the original research leading to recent developments in type 1 diabetes genetics.
We examine the translation of polygenic scores for type 1 diabetes into tools for prediction and diagnosis of type 1 diabetes, in particular, when used in combination with other biomarkers and clinical features, such as age and islet-specific autoantibodies. Furthermore, we review the description of age associations with type 1 diabetes genetic risk, and the investigation of loci linked to type 2 diabetes in progression of type 1 diabetes. Finally, we consider current limitations, including the scarcity of data from racial and ethnic minorities, and future directions.
The development of polygenic risk scores has allowed the integration of type 1 diabetes genetics into diagnosis and prediction. Emerging information on the role of specific genes in subgroups of individuals with the disease, for example, early-onset, mild autoimmunity, and so forth, is facilitating our understanding of the heterogeneity of type 1 diabetes, with the ultimate goal of using genetic information in research and clinical practice.
aRILD Level 3, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital
bNIHR Exeter Clinical Research Facility, University of Exeter Medical School
cThe Academic Renal Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
dPediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA
Correspondence to Richard A. Oram, MD, PhD, RILD Level 3, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. E-mail: R.Oram@exeter.ac.uk