Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2

We report a genomewide linkage study of type 2 diabetes ( T2D [MIM 125853]) in the Icelandic population. A list of type 2 diabetics was cross-matched with a computerized genealogical database clustering 763 type 2 diabetics into 227 families. The diabetic patients and their relatives were genotyped with 906 microsatellite markers. A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 2.90, P = 1.29 x 10(-4)) in all diabetics. Since obesity, here defined as body mass index (BMI) greater than or equal to 30 kg/m(2), is a key risk factor for the development of T2D, we studied the data either independently of BMI or by stratifying the patient group as obese ( BMI greater than or equal to 30) or nonobese (BMI < 30). A nonparametric multipoint linkage analysis yielded linkage to 5q34 - q35.2 (LOD = 3.64, P = 2.12 x 10(-5)) in the nonobese diabetics. No linkage was observed in this region for the obese diabetics. Linkage analysis conditioning on maternal transmission to the nonobese diabetics resulted in a LOD score of 3.48 (P = 3.12 x 10(-5)) in the same region, whereas conditioning on paternal transmission led to a substantial drop in the LOD score. Finally, we observed potential interactions between the 5q locus and two T2D susceptibility loci, previously mapped in other populations.