title: Genes associated with diabetes: potential for novel therapeutic targets?
abstract: BACKGROUND
  Type 2 diabetes (T2D) is a complex disease caused by an interaction between multiple genetic and environmental factors. T2D-associated loci identified by genome-wide association studies (GWAS) harbor the genes targeted by many clinically available drugs, supporting the idea that GWAS have the potential to discover novel genes for drug development.
  
  
  METHODS
  This paper outlines, among the genes at those T2D-associated loci, the functional analysis of FTO, TCF7L2, SLC30A8, and MTNR1B, illustrating caveats we should be cautious about. This paper also reviews the current status of the compounds targeting the T2D-associated genes GCK, GKRP, ADIPOQ, and ADRA2A in clinical and preclinical phases.
  
  
  CONCLUSIONS
  Functional analysis of those loci has fallen too far behind identification of T2D-associated loci. It is mandatory to define the true causal gene at the T2D-associated loci by using a variety of experimental techniques. The biggest challenge lies in the limited access to human tissues relevant to the pathogenesis of T2D. The ultimate goal of human genetic study is enabling personalized medicine based on the genetic information of individuals. More research will be needed to achieve this goal.
authors.affiliation: a Division of Diabetes, Endocrinology and Metabolism , Tokyo Medical University , 6-7-1Nishi-shinjuku, Shinjuku-ku , Tokyo 160-0023 , Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.affiliation: b Department of Diabetes and Metabolic Diseases, Graduate School of Medicine , University of Tokyo , 7-3-1 Hongo, Bunkyo-ku , Tokyo 113-8655 , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: a Division of Diabetes, Endocrinology and Metabolism , Tokyo Medical University , 6-7-1Nishi-shinjuku, Shinjuku-ku , Tokyo 160-0023 , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015195:Drug Design; D055106:Genome-Wide Association Study; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D057285:Precision Medicine
chemical_list: D007004:Hypoglycemic Agents
keywords: GWAS; association; causal variant; genetic variant; molecular target; nonsynonymous variant; regulatory variant; type 2 diabetes