Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese |
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Authors: | Toshihito Tanahashi Dai Osabe Kyoko Nomura Shuichi Shinohara Hitoshi Kato Eiichiro Ichiishi Naoto Nakamura Toshikazu Yoshikawa Yoichiro Takata Tatsuro Miyamoto Hiroshi Shiota Parvaneh Keshavarz Yuka Yamaguchi Kiyoshi Kunika Maki Moritani Hiroshi Inoue Mitsuo Itakura |
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Affiliation: | (1) Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan;(2) Department of Bioinformatics, Division of Life Science Systems, Fujitsu Limited, 1-5-2, Higashishinbashi, Minato-ku, Tokyo 105-7123, Japan;(3) Division of R&D Solution, Fujitsu Nagano Systems Engineering Limited, Nagano 380-3813, Japan;(4) Haplopharma Inc., 2-2-1, Yaesu, Chuo-ku, Tokyo 104-0028, Japan;(5) New Industry Creation Hatchery Center, Tohoku University, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan;(6) Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, 465, Kajii-cho, Hirokoji-Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan;(7) Department of Orthopedics, Institute for Health Biosciences, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan;(8) Department of Ophthalmology and Visual Neuroscience, Institute for Health Biosciences, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan |
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Abstract: | Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4α (HNF4α). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4α as a representative disease-susceptible gene, no variants of HNF4α were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni’s correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. |
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