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

Research output: Contribution to journalArticle

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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 - 01-07-2012

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Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Genome-Wide Association Study
Population
Meta-Analysis
Linkage Disequilibrium
Ethnic Groups
Genotype
Genome

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Imamura, M., Maeda, S., Yamauchi, T., Hara, K., Yasuda, K., Morizono, T., ... Kadowaki, T. (2012). A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations. Human molecular genetics, 21(13), 3042-3049. [dds113]. https://doi.org/10.1093/hmg/dds113
Imamura, Minako ; Maeda, Shiro ; Yamauchi, Toshimasa ; Hara, Kazuo ; Yasuda, Kazuki ; Morizono, Takashi ; Takahashi, Atsushi ; Horikoshi, Momoko ; Nakamura, Masahiro ; Fujita, Hayato ; Tsunoda, Tatsuhiko ; Kubo, Michiaki ; Watada, Hirotaka ; Maegawa, Hiroshi ; Okada-Iwabu, Miki ; Iwabu, Masato ; Shojima, Nobuhiro ; Ohshige, Toshihiko ; Omori, Shintaro ; Iwata, Minoru ; Hirose, Hiroshi ; Kaku, Kohei ; Ito, Chikako ; Tanaka, Yasushi ; Tobe, Kazuyuki ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Kasuga, Masato ; Kamatani, Naoyuki ; Nakamura, Yusuke ; Kadowaki, Takashi. / A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations. In: Human molecular genetics. 2012 ; Vol. 21, No. 13. pp. 3042-3049.
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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.",
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Imamura, M, Maeda, S, Yamauchi, T, Hara, K, Yasuda, K, Morizono, T, Takahashi, A, Horikoshi, M, Nakamura, M, Fujita, H, Tsunoda, T, Kubo, M, Watada, H, Maegawa, H, Okada-Iwabu, M, Iwabu, M, Shojima, N, Ohshige, T, Omori, S, Iwata, M, Hirose, H, Kaku, K, Ito, C, Tanaka, Y, Tobe, K, Kashiwagi, A, Kawamori, R, Kasuga, M, Kamatani, N, Nakamura, Y & Kadowaki, T 2012, 'A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations', Human molecular genetics, vol. 21, no. 13, dds113, pp. 3042-3049. https://doi.org/10.1093/hmg/dds113

A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations. / Imamura, Minako; Maeda, Shiro; Yamauchi, Toshimasa; Hara, Kazuo; Yasuda, Kazuki; Morizono, Takashi; Takahashi, Atsushi; Horikoshi, Momoko; Nakamura, Masahiro; Fujita, Hayato; Tsunoda, Tatsuhiko; Kubo, Michiaki; Watada, Hirotaka; Maegawa, Hiroshi; Okada-Iwabu, Miki; Iwabu, Masato; Shojima, Nobuhiro; Ohshige, Toshihiko; Omori, Shintaro; Iwata, Minoru; Hirose, Hiroshi; Kaku, Kohei; Ito, Chikako; Tanaka, Yasushi; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Kasuga, Masato; Kamatani, Naoyuki; Nakamura, Yusuke; Kadowaki, Takashi.

In: Human molecular genetics, Vol. 21, No. 13, dds113, 01.07.2012, p. 3042-3049.

Research output: Contribution to journalArticle

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T1 - A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations

AU - Imamura, Minako

AU - Maeda, Shiro

AU - Yamauchi, Toshimasa

AU - Hara, Kazuo

AU - Yasuda, Kazuki

AU - Morizono, Takashi

AU - Takahashi, Atsushi

AU - Horikoshi, Momoko

AU - Nakamura, Masahiro

AU - Fujita, Hayato

AU - Tsunoda, Tatsuhiko

AU - Kubo, Michiaki

AU - Watada, Hirotaka

AU - Maegawa, Hiroshi

AU - Okada-Iwabu, Miki

AU - Iwabu, Masato

AU - Shojima, Nobuhiro

AU - Ohshige, Toshihiko

AU - Omori, Shintaro

AU - Iwata, Minoru

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Ito, Chikako

AU - Tanaka, Yasushi

AU - Tobe, Kazuyuki

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Kasuga, Masato

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Kadowaki, Takashi

PY - 2012/7/1

Y1 - 2012/7/1

N2 - 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.

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