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=1.29×10(-4)) in all diabetics. Since obesity, here defined as body mass index (BMI) ⩾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 ⩾30) or nonobese (BMI <30). A nonparametric multipoint linkage analysis yielded linkage to 5q34–q35.2 (LOD = 3.64, P=2.12×10(-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=3.12×10(-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