Genomewide search for type 2 diabetes susceptibility genes in four American populations

Type 2 diabetes is a serious, genetically influenced disease for which no f ully effective treatments are available. Identification of biochemical or r egulatory pathways involved in the disease syndrome could lead to innovativ e therapeutic interventions, One way to identify such pathways is the genet ic analysis of families with multiple affected members where disease predis posing genes are likely to be segregating. We undertook a genomewide screen (389-395 microsatellite markers) in samples of 835 white, 591 Mexican Amer ican, 229 black, and 128 Japanese American individuals collected as part of the American Diabetes Association's GENNID study. Multipoint nonparametric linkage analyses were performed with diabetes, and diabetes or impaired gl ucose homeostasis (IH). Linkage to diabetes or IH was detected near markers D5S1404 (map position 77 cM, LOD = 2.80), D12S853 (map position 82 cM, LOD = 2.81) and GATA172D05 (X-chromosome map position 130 cM, LOD = 2.99) in w hites, near marker D3S2432 (map position 51 cM, LOD = 3.91) in Mexican Amer icans, and near marker D10S1412 (map position 14 cM, LOD = 2.39) in African Americans mainly collected in phase 1 of the study. Further analyses showe d evidence for interactions between the chromosome 5 locus and region on ch romosome 12 containing the MODY 3 gene (map position 132 cM) and between th e X-chromosome locus and region near D12S853 (map position 82 cM) in whites . Although these results were not replicated in samples collected in phase 2 of the GENNID study, the region on chromosome 12 was replicated in sample s from whites described by Bektas et al. (1999).