Role of Genetics in Type 2 Diabetes Pathogenesis

Through meta-analyses with large numbers of individuals, 53 gene loci that impact blood glucose levels were discovered or earlier findings were confirmed; 10 gene loci associated with type 2 diabetes were identified for the first time.

Genome-wide association studies (GWAS) are an effective method to detect genetic variations that play a role in the pathogenesis of diabetes mellitus. These may help identify individuals at an early stage that have an increased risk of diabetes. Epidemiologists of Helmholtz Zentrum München therefore also participate in international research consortia such as DIAGRAM (DIAbetes Genetics Replication and Meta-analysis Consortium) and MAGIC (Meta-Analyses of Glucose and Insulin-related Traits Consortium), which investigate the genetic causes of diabetes by means of GWAS, among other methods. In the consortia, the genetic association analyses are centrally coordinated to identify and specify gene variants with reference to type 2 diabetes and related metabolic disorders.

Through meta-analyses with large numbers of individuals (circa 133 000 and almost 150 000 subjects) – also using a newly developed metabochip – 53 gene regions with effects on glycemic characteristics were identified or confirmed, and ten gene loci associated with type 2 diabetes were discovered. According to the scientists involved in the studies, this high number of loci is an indication that the development of diabetes and its preliminary stages is so complex because it is based on many factors, each contributing only small effects. That is why it is foreseeable that there will be no single effective therapy for all patients with diabetes. Rather, personalized, individually tailored approaches will be needed to gain control over this major, widespread disease.

In genome-wide association studies (GWAS), state-of-the-art analysis techniques are used to detect genetic differences between healthy subjects and people with diseases such as diabetes mellitus. Thus, associations between genetic alterations and ­external characteristics can be detected, and genetic risk factors
for the development and/or course of the disease can be identified.