Clinical translation of genetic predictors for type 2 diabetes.
OBJECTIVE
To highlight recent type 2 diabetes (T2D)-associated genetic discoveries and their potential for clinical application.


RESULTS
The advent of genome-wide association screening has uncovered many loci newly associated with T2D. This review describes the techniques applied to discover novel T2D genes and compares their relative strengths, biases, and findings to date. The results of large-scale genome-wide association studies carried out since 2007 are summarized, and limitations of interpreting this preliminary data are offered. Recent studies exploring the clinical potential of these discoveries are reviewed, focusing on insights into T2D pathogenesis, risk prediction of future diabetes, and utility in guiding pharmacotherapy. The new T2D-associated loci have been implicated in beta-cell development and function, highlighting insulin secretion in the disease process. Preliminary risk prediction studies show that more loci are needed to improve T2D risk indices. Studies have also revealed that genes may play a role in the pharmacologic response to antidiabetic medications.


CONCLUSIONS
Since 2007, genome-wide association studies have rapidly increased the number of T2D-associated loci. This review summarizes the history of genetic association studies, the results from the new genome-wide association studies, and the clinical application of these findings.
Majithia
Amit R
AR
Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital, Boston, Boston, MA 02114, USA.
Florez
Jose C
JC
D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D010597:Pharmacogenetics; D011237:Predictive Value of Tests; D011379:Prognosis