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) > 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.
Reynisdottir
Inga
I
deCODE Genetics, Reykjavik, Iceland. ingar@decode.is
Thorleifsson
Gudmar
G
Benediktsson
Rafn
R
Sigurdsson
Gunnar
G
Emilsson
Valur
V
Einarsdottir
Anna Sigurlin
AS
Hjorleifsdottir
Eyrun Edda
EE
Orlygsdottir
Gudbjorg Th
GT
Bjornsdottir
Gudrun Thora
GT
Saemundsdottir
Jona
J
Halldorsson
Skarphedinn
S
Hrafnkelsdottir
Soffia
S
Sigurjonsdottir
Steinunn Bjorg
SB
Steinsdottir
Svana
S
Martin
Mitchell
M
Kochan
Jarema P
JP
Rhees
Brian K
BK
Grant
Struan F A
SF
Frigge
Michael L
ML
Kong
Augustine
A
Gudnason
Vilmundur
V
Stefansson
Kari
K
Gulcher
Jeffrey R
JR
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