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Advances in the search for the genetic determinants of type 2 diabetes have led, in recent years, to the discovery of dozens of risk loci, with many more expected to be found [1–3]. Each individual locus has a relatively small effect, increasing the risk of diabetes by ~5–40% per risk allele. Although the risk alleles themselves are common, few individuals (~10%) are homozygous at a given locus, no locus accounts for more than a fraction of a per cent of the variance in the risk of diabetes, and only a few loci have a proven function in diabetes pathogenesis [4]. It seems apparent that revelation of novel pathways determining energy metabolism will come from this era of diabetes gene discovery. However, how to apply this new knowledge to improve clinical and public health is less clear. Approaches to genetic testing and counselling for diseases with multiple common loci that exert a modest effect are not well established. The influence of genetic risk knowledge on personal health behaviours for chronic disease prevention or treatment is not known. Meanwhile, there is growing enthusiasm for the use of new genetic knowledge in disease screening and diagnostic testing [5]. In contrast to uncertainties about prevention and personalisation, the value of current genetic knowledge for prediction of diabetes risk is becoming fairly clear. In this issue of Diabetologia, Lin et al. report on a study in which they tested the ability of multiple novel type 2 diabetes risk loci to identify prevalent diabetes in over 5,000 participants of the population-based CoLaus Study [6]. They calculated an additive, weighted genetic score based on 15 single nucleotide polymorphisms (SNPs), using the lower limit of the 95% CI of the reported effect size on diabetes risk as the weight for each SNP. They tested the main effect of the genotype score on diabetes risk, and then the marginal effect after accounting for common type 2 diabetes risk factors, including age, BMI, family history of diabetes, WHR and triacylglycerol/HDLcholesterol ratio. After calculating the weighted score, they rescaled it for interpretation as odds of diabetes per risk allele. The 356 people with diabetes in the sample had a mean weighted genotype score of 15.2, whereas those without diabetes had a score of 14.3. This is a minute difference in allele count: on average, people with diabetes had just one more risk allele out of the 15 tested compared with those without diabetes. Nonetheless, the risk factoradjusted relative odds of diabetes in the fifth of the group with the highest genotype score was 2.7-fold higher than that in the fifth of the group with the lowest genotype score. Thus, it is shown that common disease risk alleles can be summed, with people at the highest end of the genetic risk distribution having a markedly elevated individual risk, especially in contrast to the low relative risk associated with individual loci. However, at the group level, the genotype Diabetologia (2009) 52:568–570 DOI 10.1007/s00125-009-1296-9

Prediction of type 2 diabetes: the dawn of polygenetic testing for complex disease