Localization of a Susceptibility Gene for Type 2 Diabetes to Chromosome 5q34–q35.2

• Published in: American journal of human genetics Vol. 73; no. 2; pp. 323 - 335
• Main 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.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.08.2003; University of Chicago Press; The American Society of Human Genetics
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Body Mass Index; Chromosome Mapping; Chromosomes, Human, Pair 10 - genetics; Chromosomes, Human, Pair 12 - genetics; Chromosomes, Human, Pair 5 - genetics; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genomic Imprinting; Humans; Iceland; Lod Score; Male; Medical sciences; Microsatellite Repeats; Middle Aged; Obesity - complications; Obesity - pathology; Pedigree; Phenotype; Iceland; Endocrinopathy; Type 2 diabetes; Human; Obesity; Family study; Pathogenesis; Nutrition disorder; Chromosome B5; Genetic determinism; Body mass index; Phenotype; Gene; Risk factor; Genetic linkage; Nutritional status; Comparative study
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/377139

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.