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 Iwata; Hiroshi Hirose; Kohei Kaku; Chikako Ito; Yasushi Tanaka; Kazuyuki Tobe; Atsunori Kashiwagi; Ryuzo Kawamori; Masato Kasuga; Naoyuki Kamatani; Yusuke Nakamura; Takashi Kadowaki

doi:10.1093/hmg/dds113

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 journal › Article › peer-review

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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 language	English
Article number	dds113
Pages (from-to)	3042-3049
Number of pages	8
Journal	Human molecular genetics
Volume	21
Issue number	13
DOIs	https://doi.org/10.1093/hmg/dds113
Publication status	Published - 07-2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Genetics(clinical)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., ... 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. Article dds113. https://doi.org/10.1093/hmg/dds113

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

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.",

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

year = "2012",

month = jul,

doi = "10.1093/hmg/dds113",

language = "English",

volume = "21",

pages = "3042--3049",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "13",

}

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

TY - JOUR

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

Y1 - 2012/7

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.

AB - 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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UR - https://www.scopus.com/inward/citedby.url?scp=84863503465&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds113

DO - 10.1093/hmg/dds113

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AN - SCOPUS:84863503465

SN - 0964-6906

VL - 21

SP - 3042

EP - 3049

JO - Human molecular genetics

JF - Human molecular genetics

IS - 13

M1 - dds113

ER -

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

Abstract

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