Genes involved in type 1 diabetes: an update

Abstract

Type 1 Diabetes (T1D) is a chronic multifactorial disease with a strong genetic component, which, through interactions with specific environmental factors, triggers disease onset. T1D typically manifests in early to mid childhood through the autoimmune destruction of pancreatic β cells resulting in a lack of insulin production. Historically, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D. With the advent of high-throughput single nucleotide polymorphism (SNP) genotyping array technologies, enabling investigators to perform high-density GWAS, many additional T1D susceptibility genes have been discovered. Indeed, recent meta-analyses of multiple datasets from independent investigators have brought the tally of well-validated T1D disease genes to almost 60. In this mini-review, we address recent advances in the genetics of T1D and provide an update on the latest susceptibility loci added to the list of genes involved in the pathogenesis of T1D.

Figure 1

The Type 1 Diabetes loci described to date: a timeline. The susceptibility loci are presented by the year they were first implicated in T1D.

Figure 2

Immune and Non-immune T1D genes. The discovery of T1D susceptibility genes started as early as 1974, with six T1D genes identified by 2006. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.

Figure 3

Pathogenesis model of T1D involves complex interactions between innate and adaptive immune cell types.