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

Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 geno...

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Published inHuman molecular genetics Vol. 23; no. 1; pp. 239 - 246
Main Authors 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
Format Journal Article
LanguageEnglish
Published England 01.01.2014
Subjects
Diabetes Mellitus, Type 2 - genetics
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Genome, Human
Genome-Wide Association Study
Guanine Nucleotide Dissociation Inhibitors - genetics
Haplotypes
Humans
Leptin - genetics
MicroRNAs - genetics
Monocarboxylic Acid Transporters - genetics
Polymorphism, Single Nucleotide
Online AccessGet full text
ISSN0964-6906
1460-2083
1460-2083
DOI10.1093/hmg/ddt399

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Abstract Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 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.
AbstractList Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 = A; risk allele frequency (RAF) = 0.080; P = 2.55 x 10 super(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 x 10 super(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 x 10 super(-13); OR = 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.
Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 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.
Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 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.Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component 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 = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 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 Teo, Yik Ying
Leung, Ting Fan
Kawamori, Ryuzo
Morizono, Takashi
Yamauchi, Toshimasa
Hu, Cheng
Hara, Kazuo
Johnson, Todd A.
Yu, Weihui
Shyong, Tai E.
Maegawa, Hiroshi
Fujita, Hayato
Kubo, Michiaki
Kadowaki, Takashi
Watada, Hirotaka
Tsunoda, Tatsuhiko
Zhang, Rong
Shojima, Nobuhiro
Iwata, Minoru
Kashiwagi, Atsunori
So, Wing Yee
Jia, Weiping
Hirose, Hiroshi
Ma, Ronald C. W.
Maeda, Shiro
Kamatani, Naoyuki
Kaku, Kohei
Wang, Jie
Tobe, Kazuyuki
Yasuda, Kazuki
Kwan, Patrick
Tanaka, Yasushi
Chan, Juliana C. N.
Imamura, Minako
Ito, Chikako
Horikoshi, Momoko
Peng, Chen
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  surname: Hara
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  organization: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan,, Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, the University of Tokyo, Tokyo 113-8655, Japan
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  fullname: Johnson, Todd A.
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  givenname: Cheng
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  organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
– sequence: 9
  givenname: Ronald C. W.
  surname: Ma
  fullname: Ma, Ronald C. W.
  organization: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China,, Li Ka Shing Institute of Health Sciences,, Hong Kong Institute of Diabetes and Obesity and
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  givenname: Minako
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  fullname: Imamura, Minako
  organization: Laboratory for Endocrinology, Metabolism, and Kidney Diseases and
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  surname: Iwata
  fullname: Iwata, Minoru
  organization: First Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan
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  surname: Tsunoda
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  organization: Laboratory for Medical Science Mathematics
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  surname: Shojima
  fullname: Shojima, Nobuhiro
  organization: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
– sequence: 15
  givenname: Wing Yee
  surname: So
  fullname: So, Wing Yee
  organization: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China,, Li Ka Shing Institute of Health Sciences,, Hong Kong Institute of Diabetes and Obesity and
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  givenname: Ting Fan
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  organization: Department of Paediatrics, Chinese University of Hong Kong, Hong Kong, China
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  organization: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
– sequence: 18
  givenname: Rong
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  organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
– sequence: 19
  givenname: Jie
  surname: Wang
  fullname: Wang, Jie
  organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
– sequence: 20
  givenname: Weihui
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  organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, China
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  organization: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23945395$$D View this record in MEDLINE/PubMed
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10.2337/db08-0906
10.1248/bpb.30.2185
10.1007/BF00280883
10.1038/ng.120
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Bengtsson Boström, Kristina
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Crawford, Gabe
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Kong, Augustine
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Roden, Michael
Sampson, Michael J
Thorleifsson, Gudmar
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Snippet Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified...
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StartPage 239
SubjectTerms Diabetes Mellitus, Type 2 - genetics
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Genome, Human
Genome-Wide Association Study
Guanine Nucleotide Dissociation Inhibitors - genetics
Haplotypes
Humans
Leptin - genetics
MicroRNAs - genetics
Monocarboxylic Acid Transporters - genetics
Polymorphism, Single Nucleotide
Title Genome-wide association study identifies three novel loci for type 2 diabetes
URI https://www.ncbi.nlm.nih.gov/pubmed/23945395
https://www.proquest.com/docview/1467634705
https://www.proquest.com/docview/1492627835
Volume 23
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