Genetic analysis of type II diabetes in Finnish populati

Human Genome Research

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Abstract

Type 2 diabetes (T2D) is one of the major causes of morbidity and mortality in the developed world. While environmental factors such as diet play a significant role, familial clustering indicates that there must be significant genetic suscepibility factors at work. For eleven years we have been engaged in a large collaborative study entitled FUSION (Finland - United States Investigation of NIDDM), in which nearly 10,000 individuals with diabetes (and suitable controls) from Finland are being studied, using careful phenotyping of diabetes and diabetes associated traits, and genome-wide genetic linkage and association. We have developed new approaches in the laboratory to achieve high throughput microsatellite and SNP genotyping, which has allowed the collection of a massive amount of data from these Finnish diabetics and their families. On the long arm of chromosome 20, a region where a dozen groups have independently shown evidence of linkage for T2D, we have identified susceptibility variants in a small region of the P2 promoter of the HNF4A transcription factor. These variants have now been confirmed by several other groups. We have also tested a number of attractive candidate genes in our large sample, and identified several that show strong evidence of association with T2D. In collaboration with the Center for Inherited Disease Research (CIDR), we have just conducted a HapMap-based genome wide association study of 1186 cases and 1171 controls, and have identified a number of possible T2D susceptibility variants that can now be assessed in a stage 2 study of another 3000 samples. With this kind of substantial progress, we are confident that the "geneticist's nightmare" (Jim Neel's description of the genetics of diabetes) may be coming to an end.