New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function.
OBJECTIVE
Over the past 18 months, the number of gene loci robustly associated with type 2 diabetes has risen from three to 18. In this study, we focus on explaining the genome-wide approach that has led to most of these discoveries and discuss some of the early insights the new gene loci have provided into the aetiology of type 2 diabetes.


RESULTS
Recent genome-wide association studies have provided an important resource for furthering our understanding of type 2 diabetes disease mechanisms. Genes previously unsuspected of playing a role in diabetes are now implicated in the disease process. These include genes in cell cycling control (CDKN2A/2B, CDKAL1), transcription factors (TCF7L2, HHEX), and ion channels (SLC30A8). These variants are all associated with insulin-secretory defects in the general population and show little if any relationship to insulin resistance. Two common variants (near or in FTO and MC4R) alter diabetes risk through a primary effect on obesity.


CONCLUSIONS
Recent genome-wide association studies show that there are now 18 gene loci associated with the risk of type 2 diabetes. Most of these T2D gene loci affect insulin secretion.
Perry
John R B
JR
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.
Frayling
Timothy M
TM
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*
D007328:Insulin