A new era in finding Type 2 diabetes genes-the unusual suspects.

In 1988 the task of identifying Type 2 diabetes genes was described as a nightmare. For the next 17 years this proved to be largely correct. In the meantime the prevalence of Type 2 diabetes rose sharply due to non-genetic factors, compounding the problem of trying to find genes. Despite a huge amount of effort, progress was disappointing and only two genes, PPARG and KCNJ11, were confirmed beyond doubt as Type 2 diabetes risk factors in multiple studies. The reasons for this have been well documented and mainly consist of the use of inappropriate levels of statistical inference given the many hundreds of thousands of potential risk polymorphisms in the genome and their small effect sizes. The good news is that these problems are now surmountable and prospects for finding many more genes are bright. This year saw the identification of a third gene, TCF7L2, that has a greater impact on risk than the first two and provided important lessons for Type 2 diabetes genetic studies. The most important of these lessons was that previously unsuspected genes may be involved. In this review I discuss why this year is the start of a new era in our understanding of Type 2 diabetes genes and how this may lead to improved patient care.