Mapping Genes Influencing Type 2 Diabetes Risk and BMI in Japanese Subjects
- Naoko Iwasaki1,
- Nancy J. Cox2,
- Yan-Qing Wang2,
- Peter E.H. Schwarz2,
- Graeme I. Bell2,
- Masashi Honda3,
- Mitsuo Imura4,
- Makiko Ogata1,
- Masayuki Saito5,
- Naoyuki Kamatani5 and
- Yasuhiko Iwamoto1
- 1Diabetes Center, Tokyo Women’s Medical University, Tokyo, Japan
- 2Departments of Human Genetics, Medicine, and Biochemistry and Molecular Biology, the University of Chicago, Chicago, Illinois
- 3Department of Diabetes, Shiseikai Daini Hospital, Tokyo, Japan
- 4Department of Endocrinology, Yaizu Citizens Hospital, Shizuoka, Japan
- 5Division of Statistical Genetics, Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
We have carried out an autosomal genome scan for genes contributing to the development of type 2 diabetes and affecting BMI in the Japanese population (164 families, 256 affected sib-pairs). We found 12 regions that showed nominally significant multipoint evidence of linkage with type 2 diabetes (i.e. logarithm of odds [LOD] score >0.59, P < 0.05): chromosome 1 29.9 cM; chromosome 2 169.6 and 236.8 cM; chromosome 4 104.9 cM; chromosome 5 114.8 cM; chromosome 6 42.3 cM; chromosome 8 15.3 and 93.3 cM; chromosome 9 140.0 cM; chromosome 11 131.6 cM; chromosome 17 36.1 cM; and chromosome 21 48.0 cM. Twelve regions showed nominal multipoint evidence for linkage with log-transformed BMI (lnBMI): chromosome 2 167.9 and 210.5 cM; chromosome 3 185.7 cM; chromosome 4 118.9 and 145.6 cM; chromosome 5 131.9 cM; chromosome 7 7.4 cM; chromosome 10 70.0 cM; chromosome 15 12.8 cM; chromosome 16 30.0 cM; and chromosome 17 47.8 and 100.2 cM. Although none of the regions achieved genome-wide levels of significance, simulation studies showed that we observed more linkage signals than expected if there were no loci contributing to type 2 diabetes or BMI. Eight of the regions showing nominal evidence for linkage with type 2 diabetes have been reported in other genome scans, and seven of the regions showing linkage with lnBMI have shown linkage with BMI and BMI-related traits in other studies. Thus, our results may replicate findings in other studies. They may also indicate new regions of the genome that are involved in the regulation of blood glucose levels or body weight.
Address correspondence and reprint requests to Dr. Naoko Iwasaki, Diabetes Center, Tokyo Women’s Medical University, 8–1 Kawado-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail:.
Received for publication 10 August 2002 and accepted in revised form 8 October 2002.
Additional information can be found in an online appendix at http://diabetes.diabetesjournals.org.
ASP, affected sib-pair; lnBMI, log-transformed BMI; LOD, logarithm of odds; MLS, maximum likelihood score; MODY, maturity-onset diabetes of the young; NPL, nonparametric linkage; QTL, quantitative trait locus.