Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-11

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

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 4alpha (HNF4alpha). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4alpha as a representative disease-susceptible gene, no variants of HNF4alpha 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. More... »

PAGES

527-542

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-006-0231-0

    DOI

    http://dx.doi.org/10.1007/s00439-006-0231-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1015358596

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/16955255


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    426 schema:name New Industry Creation Hatchery Center, Tohoku University, Aramaki, Aoba-ku, Sendai, 980-8579, Miyagi, Japan
    427 rdf:type schema:Organization
     




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