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
- Yasumichi Mori1,
- Shuichi Otabe1,
- Christian Dina2,
- Kazuki Yasuda1,
- Céline Populaire2,
- Cécile Lecoeur2,
- Vincent Vatin2,
- Emmanuelle Durand2,
- Kazuo Hara1,
- Terumasa Okada1,
- Kazuyuki Tobe1,
- Philippe Boutin2,
- Takashi Kadowaki1 and
- Philippe Froguel23
- 1Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- 2Institute of Biology-Centre National de Research Scientifique 8090, Institut Pasteur de Lille, Lille, France
- 3Barts and the London Genome Centre, Queen Mary and Westfield College, London, U.K.
Abstract
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-4α [HNF-4α]). 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.
Footnotes
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Address correspondence and reprint requests to Philippe Froguel, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019, Lille, France. E-mail: philippe.froguel{at}mail-good.pasteur-lille.fr.
Received for publication 31 July 2001 and accepted in revised form 4 January 2002.
Y.M., S.O., C.D., and K.Y. contributed equally to this work.
GK, glucokinase; IRS-1, insulin receptor substrate-1; LOD, logarithm of odds; MLS, maximum LOD score; QTL, quantitative trait loci.
- DIABETES
