Progress in genetics of type 2 diabetes and diabetic complications

Abstract

Type 2 diabetes results from a complex interaction between genetic and environmental factors. Precision medicine for type 2 diabetes using genetic data is expected to predict the risk of developing diabetes and complications and to predict the effects of medications and life-style intervention more accurately for individuals. Genome-wide association studies (GWAS) have been conducted in European and Asian populations and new genetic loci have been identified that modulate the risk of developing type 2 diabetes. Novel loci were discovered by GWAS in diabetic complications with increasing sample sizes. Large-scale genome-wide association analysis and polygenic risk scores using biobank information is making it possible to predict the development of type 2 diabetes. In the ADVANCE clinical trial of type 2 diabetes, a multi-polygenic risk score was useful to predict diabetic complications and their response to treatment. Proteomics and metabolomics studies have been conducted and have revealed the associations between type 2 diabetes and inflammatory signals and amino acid synthesis. Using multi-omics analysis, comprehensive molecular mechanisms have been elucidated to guide the development of targeted therapy for type 2 diabetes and diabetic complications.

Keywords: Diabetic complications; Precision medicine; Type 2 diabetes.

Figure 1

Timeline of key discoveries of type 2 diabetes genetics by genome‐wide association study (GWAS). GWAS identified genetic loci for type 2 diabetes at the genome‐wide significance level (P < 5.0 × 10⁻⁸). Cumulative count of discovered loci per year are presented.

Figure 2

Timeline of key discoveries of genetics of diabetic kidney disease by genome‐wide association study (GWAS). GWAS identified genetic loci for type 2 diabetes at the genome‐wide significance level (P < 5.0 × 10⁻⁸). Cumulative count of discovered loci per year are presented.

Figure 3

Timeline of key discoveries of genetics of diabetic retinopathy by genome‐wide association study (GWAS). GWAS identified genetic loci for type 2 diabetes at the genome‐wide significance level (P < 5.0 × 10⁻⁸). Cumulative count of discovered loci per year are presented.

Figure 4

Timeline of key discoveries of genetics of diabetic neuropathy by genome‐wide association study (GWAS). GWAS identified genetic loci for type 2 diabetes at the genome‐wide significance level (P < 5.0 × 10⁻⁸). Cumulative count of discovered loci per year are presented.

Figure 5

Predicting diabetes and diabetic complications using polygenic risk score. Intensive therapy and/or life‐style intervention for high‐risk group reduces the development of diabetes and diabetic complications compared with standard therapy and/or life‐style intervention for all groups.