Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p.
The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4alpha [HNF-4alpha]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.
Mori
Yasumichi
Y
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Otabe
Shuichi
S
Dina
Christian
C
Yasuda
Kazuki
K
Populaire
Céline
C
Lecoeur
Cécile
C
Vatin
Vincent
V
Durand
Emmanuelle
E
Hara
Kazuo
K
Okada
Terumasa
T
Tobe
Kazuyuki
K
Boutin
Philippe
P
Kadowaki
Takashi
T
Froguel
Philippe
P
D000328:Adult; D017668:Age of Onset; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D002890:Chromosomes, Human, Pair 20; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009679:Nuclear Family; D010750:Phosphoproteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D010750:Phosphoproteins; D014157:Transcription Factors