Large case-control studies using whole genome arrays of single nucleotide polymorphisms (genome-wide association studies) have identified multiple common risk alleles for type 2 diabetes, many of which reside in or near genes not previously implicated in the pathogenesis of diabetes,9 10 11 12 in addition to confirming loci identified by previous candidate gene studies.13 14 Around 20 single nucleotide polymorphisms associated with type 2 diabetes have been identified, for which the findings from the discovery study have been independently replicated in additional datasets and the effect sizes evaluated precisely by meta-analysis (as detailed in web table A).15 16 17 18 For all loci identified to date, effect sizes have been modest, with odds ratios for risk of type 2 diabetes ranging from 1.37 for single nucleotide polymorphisms in the gene TCF7L2 to 1.09 for those in the gene ADAMTS9,18 raising the question of whether information on genotype would be useful for prediction of risk. Moreover, risk alleles have been discovered mainly by using case-control studies, which, although efficient for the discovery of disease associated single nucleotide polymorphisms, are suboptimal for
