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World J Diabetes. Aug 15, 2013; 4(4): 114-123
Published online Aug 15, 2013. doi: 10.4239/wjd.v4.i4.114
Genetics of type 2 diabetes
Omar Ali
Omar Ali, Medical College of Wisconsin, Milwaukee, WI 53226, United States
Author contributions: Ali O reviewed the published literature and wrote the article in its entirety.
Correspondence to: Omar Ali, MD, Medical College of Wisconsin, Milwaukee, 8701 W Watertown Plank Rd, WI 53226, United States.
Telephone: +1-414-2666750 Fax: +1-414-2666749
Received: March 3, 2013
Revised: June 1, 2013
Accepted: July 18, 2013
Published online: August 15, 2013

Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this “missing heritability”, including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.

Keywords: Type 2 diabetes, Genetics, TCF7L2, Genome-wide association studies, Heritability

Core tip: We review the history and the current state of knowledge regarding the genetic component of type 2 diabetes risk. Genes like TCF7L2 that have been replicated in multiple studies are discussed in detail. The significance of these findings is discussed and gaps in our knowledge are identified, as are avenues for future research.