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

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Authors
Reynisdottir, Inga
Thorleifsson, Gudmar
Benediktsson, Rafn
Sigurdsson, Gunnar
Emilsson, Valur
Einarsdottir, Anna Sigurlin
Hjorleifsdottir, Eyrun Edda
Orlygsdottir, Gudbjorg Th
Bjornsdottir, Gudrun Thora
Saemundsdottir, Jona
Halldorsson, Skarphedinn
Hrafnkelsdottir, Soffia
Sigurjonsdottir, Steinunn Bjorg
Steinsdottir, Svana
Martin, Mitchell
Kochan, Jarema P
Rhees, Brian K
Grant, Struan F A
Frigge, Michael L
Kong, Augustine
Gudnason, Vilmundur
Stefansson, Kari
Gulcher, Jeffrey R
Issue Date
2003-08-01

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Citation
Am. J. Hum. Genet. 2003, 73(2):323-35
Abstract
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) > or =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 > or =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.
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http://www.journals.uchicago.edu/AJHG/journal/issues/v73n2/35005/35005.html
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