title: Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese.
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.
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Tokushima, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Dai
authors.initials: D
authors.lastname: Osabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nomura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shinohara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takata
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiota
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Keshavarz
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kunika
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006239:Haplotypes; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4