A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations

Minako Imamura, Shiro Maeda, Toshimasa Yamauchi, Kazuo Hara, Kazuki Yasuda, Takashi Morizono, Atsushi Takahashi, Momoko Horikoshi, Masahiro Nakamura, Hayato Fujita, Tatsuhiko Tsunoda, Michiaki Kubo, Hirotaka Watada, Hiroshi Maegawa, Miki Okada-Iwabu, Masato Iwabu, Nobuhiro Shojima, Toshihiko Ohshige, Shintaro Omori, Minoru IwataHiroshi Hirose, Kohei Kaku, Chikako Ito, Yasushi Tanaka, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Masato Kasuga, Naoyuki Kamatani, Yusuke Nakamura, Takashi Kadowaki

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69 Citations (Scopus)

Abstract

To identify a novel susceptibility locus for type 2 diabetes, we performed an imputation-based, genome-wide association study (GWAS) in a Japanese population using newly obtained imputed-genotype data for 2 229 890 single-nucleotide polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS data in the same samples (stage 1: 4470 type 2 diabetes versus 3071 controls). We directly genotyped 43 new SNPs with P-values of <10-4 in a part of stage-1 samples (2692 type 2 diabetes versus 3071 controls), and the associations of validated SNPs were evaluated in another 11 139 Japanese individuals (stage 2: 7605 type 2 diabetes versus 3534 controls). Combined meta-analysis using directly genotyped data for stages 1 and 2 revealed that rs515071 in ANK1 and rs7656416 near MGC21675 were associated with type 2 diabetes in the Japanese population at the genome-wide significant level (P < 5 × 10-8). The association of rs515071 was also observed in European GWAS data (combined P for all populations = 6.14 × 10-10). Rs7656416 was in linkage disequilibrium to rs6815464, which had recently been identified as a top signal in a meta-analysis of East Asian GWAS for type 2 diabetes (r2 = 0.76 in stage 2). The association of rs7656416 with type 2 diabetes disappeared after conditioning on rs6815464. These results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups. The signal of association was weaker in the directly genotyped data, so the improvement in signal indicates the importance of imputation in this particular case.

Original languageEnglish
Article numberdds113
Pages (from-to)3042-3049
Number of pages8
JournalHuman molecular genetics
Volume21
Issue number13
DOIs
Publication statusPublished - 2012 Jul

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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