title: Genetics of type 2 diabetes: pathophysiologic and clinical relevance.
abstract: BACKGROUND
  Recent genome-wide association studies enlarged our knowledge about the genetic background of type 2 diabetes.
  
  
  OBJECTIVE
  This review provides an overview of the role of these novel genetic findings for the pathophysiology, prediction and treatment of type 2 diabetes.
  
  
  RESULTS
  The genetic susceptibility to type 2 diabetes appears to be determined by many common variants in multiple gene loci with low effect sizes. Although at least 36 diabetes-associated genes were identified, only about 10% of the heritability of type 2 diabetes can be explained. Most of the discovered gene variants have been linked to beta-cell dysfunction rather than insulin resistance, which might challenge established thinking of type 2 diabetes as a predominant disorder of insulin action. Genetic data can lead to statistically significant, but not to clinically relevant contributions to risk prediction for type 2 diabetes. Nevertheless, preliminary evidence suggests interactions between genotypes and response to lifestyle changes or drug treatment.
  
  
  CONCLUSIONS
  Future studies need to target the issue of hidden heritability and to detect the causal gene variants within the identified gene loci. Improved understanding of the genetic contribution to type 2 diabetes may then help addressing the questions whether genotyping is useful to predict individual diabetes risk, identifies individual responsiveness to preventive and therapeutic interventions or at least allows for breaking down type 2 diabetes into smaller, clinically meaningful subtypes.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D018570:Risk Assessment
chemical_list: D007328:Insulin