Genome-wide association study identifies three novel loci for type 2 diabetes

Kazuo Hara, Hayato Fujita, Todd A. Johnson, Toshimasa Yamauchi, Kazuki Yasuda, Momoko Horikoshi, Chen Peng, Cheng Hu, Ronald C.W. Ma, Minako Imamura, Minoru Iwata, Tatsuhiko Tsunoda, Takashi Morizono, Nobuhiro Shojima, Wing Yee So, Ting Fan Leung, Patrick Kwan, Rong Zhang, Jie Wang, Weihui Yu & 17 others Hiroshi Maegawa, Hiroshi Hirose, Kohei Kaku, Chikako Ito, Hirotaka Watada, Yasushi Tanaka, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Weiping Jia, Juliana C.N. Chan, Yik Ying Teo, Tai E. Shyong, Naoyuki Kamatani, Michiaki Kubo, Shiro Maeda, Takashi Kadowaki

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Although over 60loci for type 2 diabetes (T2D) havebeenidentified, there still remains a large geneticcomponent to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele 5 A; risk allele frequency (RAF) 5 0.080; P 5 2.55 × 10-13; odds ratio (OR) 5 1.17], GPSM1 [rs11787792; risk allele 5 A; RAF 5 0.874; P 5 1.74 × 10-10; OR 5 1.15] and SLC16A13 (rs312457; risk allele 5 G; RAF 5 0.078; P 5 7.69 × 10-13; OR 5 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

Original languageEnglish
Article numberddt399
Pages (from-to)239-246
Number of pages8
JournalHuman molecular genetics
Volume23
Issue number1
DOIs
Publication statusPublished - 01-01-2014

Fingerprint

Genome-Wide Association Study
Type 2 Diabetes Mellitus
Gene Frequency
Alleles
Odds Ratio
Genome
Haplotypes
Single Nucleotide Polymorphism
Genotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Hara, K., Fujita, H., Johnson, T. A., Yamauchi, T., Yasuda, K., Horikoshi, M., ... Kadowaki, T. (2014). Genome-wide association study identifies three novel loci for type 2 diabetes. Human molecular genetics, 23(1), 239-246. [ddt399]. https://doi.org/10.1093/hmg/ddt399
Hara, Kazuo ; Fujita, Hayato ; Johnson, Todd A. ; Yamauchi, Toshimasa ; Yasuda, Kazuki ; Horikoshi, Momoko ; Peng, Chen ; Hu, Cheng ; Ma, Ronald C.W. ; Imamura, Minako ; Iwata, Minoru ; Tsunoda, Tatsuhiko ; Morizono, Takashi ; Shojima, Nobuhiro ; So, Wing Yee ; Leung, Ting Fan ; Kwan, Patrick ; Zhang, Rong ; Wang, Jie ; Yu, Weihui ; Maegawa, Hiroshi ; Hirose, Hiroshi ; Kaku, Kohei ; Ito, Chikako ; Watada, Hirotaka ; Tanaka, Yasushi ; Tobe, Kazuyuki ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Jia, Weiping ; Chan, Juliana C.N. ; Teo, Yik Ying ; Shyong, Tai E. ; Kamatani, Naoyuki ; Kubo, Michiaki ; Maeda, Shiro ; Kadowaki, Takashi. / Genome-wide association study identifies three novel loci for type 2 diabetes. In: Human molecular genetics. 2014 ; Vol. 23, No. 1. pp. 239-246.
@article{070418c16f2d4c2299103f3818dd6943,
title = "Genome-wide association study identifies three novel loci for type 2 diabetes",
abstract = "Although over 60loci for type 2 diabetes (T2D) havebeenidentified, there still remains a large geneticcomponent to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele 5 A; risk allele frequency (RAF) 5 0.080; P 5 2.55 × 10-13; odds ratio (OR) 5 1.17], GPSM1 [rs11787792; risk allele 5 A; RAF 5 0.874; P 5 1.74 × 10-10; OR 5 1.15] and SLC16A13 (rs312457; risk allele 5 G; RAF 5 0.078; P 5 7.69 × 10-13; OR 5 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.",
author = "Kazuo Hara and Hayato Fujita and Johnson, {Todd A.} and Toshimasa Yamauchi and Kazuki Yasuda and Momoko Horikoshi and Chen Peng and Cheng Hu and Ma, {Ronald C.W.} and Minako Imamura and Minoru Iwata and Tatsuhiko Tsunoda and Takashi Morizono and Nobuhiro Shojima and So, {Wing Yee} and Leung, {Ting Fan} and Patrick Kwan and Rong Zhang and Jie Wang and Weihui Yu and Hiroshi Maegawa and Hiroshi Hirose and Kohei Kaku and Chikako Ito and Hirotaka Watada and Yasushi Tanaka and Kazuyuki Tobe and Atsunori Kashiwagi and Ryuzo Kawamori and Weiping Jia and Chan, {Juliana C.N.} and Teo, {Yik Ying} and Shyong, {Tai E.} and Naoyuki Kamatani and Michiaki Kubo and Shiro Maeda and Takashi Kadowaki",
year = "2014",
month = "1",
day = "1",
doi = "10.1093/hmg/ddt399",
language = "English",
volume = "23",
pages = "239--246",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "1",

}

Hara, K, Fujita, H, Johnson, TA, Yamauchi, T, Yasuda, K, Horikoshi, M, Peng, C, Hu, C, Ma, RCW, Imamura, M, Iwata, M, Tsunoda, T, Morizono, T, Shojima, N, So, WY, Leung, TF, Kwan, P, Zhang, R, Wang, J, Yu, W, Maegawa, H, Hirose, H, Kaku, K, Ito, C, Watada, H, Tanaka, Y, Tobe, K, Kashiwagi, A, Kawamori, R, Jia, W, Chan, JCN, Teo, YY, Shyong, TE, Kamatani, N, Kubo, M, Maeda, S & Kadowaki, T 2014, 'Genome-wide association study identifies three novel loci for type 2 diabetes', Human molecular genetics, vol. 23, no. 1, ddt399, pp. 239-246. https://doi.org/10.1093/hmg/ddt399

Genome-wide association study identifies three novel loci for type 2 diabetes. / Hara, Kazuo; Fujita, Hayato; Johnson, Todd A.; Yamauchi, Toshimasa; Yasuda, Kazuki; Horikoshi, Momoko; Peng, Chen; Hu, Cheng; Ma, Ronald C.W.; Imamura, Minako; Iwata, Minoru; Tsunoda, Tatsuhiko; Morizono, Takashi; Shojima, Nobuhiro; So, Wing Yee; Leung, Ting Fan; Kwan, Patrick; Zhang, Rong; Wang, Jie; Yu, Weihui; Maegawa, Hiroshi; Hirose, Hiroshi; Kaku, Kohei; Ito, Chikako; Watada, Hirotaka; Tanaka, Yasushi; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Jia, Weiping; Chan, Juliana C.N.; Teo, Yik Ying; Shyong, Tai E.; Kamatani, Naoyuki; Kubo, Michiaki; Maeda, Shiro; Kadowaki, Takashi.

In: Human molecular genetics, Vol. 23, No. 1, ddt399, 01.01.2014, p. 239-246.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study identifies three novel loci for type 2 diabetes

AU - Hara, Kazuo

AU - Fujita, Hayato

AU - Johnson, Todd A.

AU - Yamauchi, Toshimasa

AU - Yasuda, Kazuki

AU - Horikoshi, Momoko

AU - Peng, Chen

AU - Hu, Cheng

AU - Ma, Ronald C.W.

AU - Imamura, Minako

AU - Iwata, Minoru

AU - Tsunoda, Tatsuhiko

AU - Morizono, Takashi

AU - Shojima, Nobuhiro

AU - So, Wing Yee

AU - Leung, Ting Fan

AU - Kwan, Patrick

AU - Zhang, Rong

AU - Wang, Jie

AU - Yu, Weihui

AU - Maegawa, Hiroshi

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Ito, Chikako

AU - Watada, Hirotaka

AU - Tanaka, Yasushi

AU - Tobe, Kazuyuki

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Jia, Weiping

AU - Chan, Juliana C.N.

AU - Teo, Yik Ying

AU - Shyong, Tai E.

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

AU - Maeda, Shiro

AU - Kadowaki, Takashi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Although over 60loci for type 2 diabetes (T2D) havebeenidentified, there still remains a large geneticcomponent to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele 5 A; risk allele frequency (RAF) 5 0.080; P 5 2.55 × 10-13; odds ratio (OR) 5 1.17], GPSM1 [rs11787792; risk allele 5 A; RAF 5 0.874; P 5 1.74 × 10-10; OR 5 1.15] and SLC16A13 (rs312457; risk allele 5 G; RAF 5 0.078; P 5 7.69 × 10-13; OR 5 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

AB - Although over 60loci for type 2 diabetes (T2D) havebeenidentified, there still remains a large geneticcomponent to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele 5 A; risk allele frequency (RAF) 5 0.080; P 5 2.55 × 10-13; odds ratio (OR) 5 1.17], GPSM1 [rs11787792; risk allele 5 A; RAF 5 0.874; P 5 1.74 × 10-10; OR 5 1.15] and SLC16A13 (rs312457; risk allele 5 G; RAF 5 0.078; P 5 7.69 × 10-13; OR 5 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

UR - http://www.scopus.com/inward/record.url?scp=84890397941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890397941&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddt399

DO - 10.1093/hmg/ddt399

M3 - Article

VL - 23

SP - 239

EP - 246

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 1

M1 - ddt399

ER -

Hara K, Fujita H, Johnson TA, Yamauchi T, Yasuda K, Horikoshi M et al. Genome-wide association study identifies three novel loci for type 2 diabetes. Human molecular genetics. 2014 Jan 1;23(1):239-246. ddt399. https://doi.org/10.1093/hmg/ddt399