Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan

Horikawa, Yukio; Miyake, Kazuaki; Yasuda, Kazuki; Enya, Mayumi; Hirota, Yushi; Yamagata, Kazuya; Hinokio, Yoshinori; Oka, Yoshitomo; Iwasaki, Naoko; Iwamoto, Yasuhiko; Yamada, Yoshio; Seino, Yutaka; Maegawa, Hiroshi; Kashiwagi, Atsunori; Yamamoto, Ken; Tokunaga, Katsushi; Takeda, Jun; Kasuga, Masato

doi:10.1210/jc.2008-0452

Cited by 127 publications

(96 citation statements)

References 18 publications

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“…The overall frequency of the A allele was 54.1%, which is higher than that in the European population and similar to that in the Han Chinese and Japanese population reported previously. 8,9,18 The A allele of GCKR rs780094 was associated with a reduced risk of T2DM (OR¼0.711 (95% confidence interval¼0.589-0.859), P¼4.2Â10 À4 ) as previously reported in a Danish study. 5 To further clarify T2DM susceptibility, a meta-analysis combining previous reports, from which we were able to use genotype frequency data, was performed.…”

Section: Resultssupporting

confidence: 76%

“…5 To further clarify T2DM susceptibility, a meta-analysis combining previous reports, from which we were able to use genotype frequency data, was performed. In a meta-analysis combining a previous Japanese study (Table 2), 9 the A allele of GCKR rs780094 was found to be associated with a reduced risk of T2DM (OR¼0.858 (95% confidence interval¼0.788-0.934), P¼4.0Â10 À4 ). Furthermore, a meta-analysis combining the Japanese and Danish studies also showed this association (OR¼0.898 (95% confidence interval¼0.854-0.945), P¼3.2Â10 À5 ).…”

Section: Resultsmentioning

confidence: 92%

“…8 In a Japanese study, a significant association of the A allele of GCKR rs780094 with lower plasma TG levels and a marginal association with T2DM were reported. 9 Rare mutations in the human glucokinase (GCK) gene have been reported to be a cause of maturity-onset diabetes of the young. 10 GCK rs179988, which is located in the promoter region of GCK, was reported to be associated with FPG 11 and T2DM.…”

Section: Introductionmentioning

confidence: 99%

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The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population

et al. 2010

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It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in Japanese subjects by analyzing 488 cases and 398 controls. A meta-analysis was performed involving two previous association studies. We also analyzed the association between the single-nucleotide polymorphism and clinical parameters in the general Japanese population (n¼1854). In the case-control study, the A allele of GCKR rs780094 was associated with a reduced risk of T2DM (odds ratio¼0.711 (95% confidence interval¼0.589-0.859), P¼4.2Â10 À4 ). A meta-analysis confirmed the association of GCKR rs780094 with T2DM susceptibility. In the general Japanese population, subjects with the A/A genotype had lower levels of FPG, fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the G/G genotype. Conversely, subjects with the A/A genotype had higher levels of TG than those with the G/G genotype. We replicated GCKR rs780094 as a marker of T2DM susceptibility in Japanese subjects. This suggests that GCKR rs780094 is a common variant for T2DM susceptibility in various ethnic groups.

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Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population

et al. 2010

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“…In addition, Japanese research groups, including ours, recently identified an association of the potassium voltage-gated channel KQT-like subfamily member 1 (KCNQ1) locus with type 2 diabetes in populations of East Asian descent [8,9]. Because most of these loci have also been shown to be associated with type 2 diabetes in other ethnic populations [8][9][10][11][12][13], these loci could be considered as convincing susceptibility genes for type 2 diabetes across different ethnicities.…”

Section: Introductionmentioning

confidence: 93%

Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals

et al. 2009

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Aims/hypothesis Additional susceptibility loci for type 2 diabetes have been identified by a meta-analysis of genome-wide association studies (GWASs) in European populations. To examine further the roles of these new loci, we performed a replication study for the association of these single-nucleotide polymorphism (SNP) loci with the disease in three independent Japanese populations. Methods We genotyped seven of the 11 SNPs that emerged in stage 2 of the meta-analysis for European GWASs (rs864745 in JAZF1, rs12779790 near CDC123/CAMK1D, rs7961581 near TSPAN8/LGR5, rs4607103 near ADAMTS9, rs10923931 in NOTCH2, rs1153188 near DCD and rs9472138 near VEGFA) for three independent Japanese populations (first set, 1,630 type 2 diabetes patients vs 1,064 controls; second set, 1,272 type 2 diabetes patients vs 856 controls; third set, 486 type 2 diabetes patients vs 936 controls) using a TaqMan assay. The association of the SNP loci in each population was analysed using a logistic regression analysis, adjusting for age, sex and BMI, and the data were evaluated by a meta-analysis. Results A meta-analysis for the three case-control studies identified a nominal association of rs864745 in JAZF1 with type 2 diabetes (OR 1.148, 95% CI 1.034-1.275, p= Diabetologia

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“…35) and has been replicated in subsequent studies in many different ethnicities. [8][9][10][11][12][13][14][15][16] The association of other newly emerged GWAS loci, such as IGF2BP2, CDKAL1, CDKN2A/B, HHEX, SLC30A8 and KCNJ11, was replicated in Japanese; 17,18 IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A/B and FTO in Asians from Hong Kong and Korea; 19 IGF2BP2, CDKAL1, CDKN2A/B, HHEX and SLC30A8 in Han Chinese; 20 and IGF2BP2, PPARG2 and FTO in Indian Sikhs. 21 More recently, a meta-analysis of three large GWA studies by the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium identified six additional T2D loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) to be strongly associated with increased susceptibility to T2D with modest ORs (1.15À1.3).…”

Section: Introductionmentioning

confidence: 96%

Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs

et al. 2009

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A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P¼0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P¼0.030) and in T2D cases (P¼0.009), as well as in the combined sample (P¼0.003) after adjusting for covariates. Evidence of impaired b-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P¼0.008) and in a combined cohort (P¼0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting b-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent.

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Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan

Abstract: Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans.

Cited by 127 publications

References 18 publications

The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population

The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population

Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals

Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs

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