title: Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2.
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.
authors.affiliation: deCODE Genetics, Reykjavik, Iceland. ingar@decode.is
authors.forename: Inga
authors.initials: I
authors.lastname: Reynisdottir
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Rafn
authors.initials: R
authors.lastname: Benediktsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sigurdsson
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Anna Sigurlin
authors.initials: AS
authors.lastname: Einarsdottir
authors.forename: Eyrun Edda
authors.initials: EE
authors.lastname: Hjorleifsdottir
authors.forename: Gudbjorg Th
authors.initials: GT
authors.lastname: Orlygsdottir
authors.forename: Gudrun Thora
authors.initials: GT
authors.lastname: Bjornsdottir
authors.forename: Jona
authors.initials: J
authors.lastname: Saemundsdottir
authors.forename: Skarphedinn
authors.initials: S
authors.lastname: Halldorsson
authors.forename: Soffia
authors.initials: S
authors.lastname: Hrafnkelsdottir
authors.forename: Steinunn Bjorg
authors.initials: SB
authors.lastname: Sigurjonsdottir
authors.forename: Svana
authors.initials: S
authors.lastname: Steinsdottir
authors.forename: Mitchell
authors.initials: M
authors.lastname: Martin
authors.forename: Jarema P
authors.initials: JP
authors.lastname: Kochan
authors.forename: Brian K
authors.initials: BK
authors.lastname: Rhees
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Michael L
authors.initials: ML
authors.lastname: Frigge
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007055:Iceland; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000473:pathology; D010375:Pedigree; D010641:Phenotype