Replication study of the association of rs7578597 in THADA, rs10886471 in GRK5, and rs7403531 in RASGRP1 with susceptibility to type 2 diabetes among a Japanese population

Kensuke Sakai, Minako Imamura, Yasushi Tanaka, Minoru Iwata, Hiroshi Hirose, Kohei Kaku, Hiroshi Maegawa, Hirotaka Watada, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Shiro Maeda

Research output: Contribution to journalArticle

Abstract

Aims: To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods: We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results: Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 % confidence interval = 0.33–0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions: The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.

Original languageEnglish
Pages (from-to)306-312
Number of pages7
JournalDiabetology International
Volume6
Issue number4
DOIs
Publication statusPublished - 2015 Dec 1

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Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Population
Gene Frequency
Control Groups
Body Mass Index
Logistic Models
Odds Ratio
Regression Analysis
Confidence Intervals

Keywords

  • Genetic association studies
  • Japanese
  • Single nucleotide polymorphism
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Replication study of the association of rs7578597 in THADA, rs10886471 in GRK5, and rs7403531 in RASGRP1 with susceptibility to type 2 diabetes among a Japanese population. / Sakai, Kensuke; Imamura, Minako; Tanaka, Yasushi; Iwata, Minoru; Hirose, Hiroshi; Kaku, Kohei; Maegawa, Hiroshi; Watada, Hirotaka; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Maeda, Shiro.

In: Diabetology International, Vol. 6, No. 4, 01.12.2015, p. 306-312.

Research output: Contribution to journalArticle

Sakai, Kensuke ; Imamura, Minako ; Tanaka, Yasushi ; Iwata, Minoru ; Hirose, Hiroshi ; Kaku, Kohei ; Maegawa, Hiroshi ; Watada, Hirotaka ; Tobe, Kazuyuki ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Maeda, Shiro. / Replication study of the association of rs7578597 in THADA, rs10886471 in GRK5, and rs7403531 in RASGRP1 with susceptibility to type 2 diabetes among a Japanese population. In: Diabetology International. 2015 ; Vol. 6, No. 4. pp. 306-312.
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abstract = "Aims: To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods: We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results: Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 {\%} confidence interval = 0.33–0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions: The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.",
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T1 - Replication study of the association of rs7578597 in THADA, rs10886471 in GRK5, and rs7403531 in RASGRP1 with susceptibility to type 2 diabetes among a Japanese population

AU - Sakai, Kensuke

AU - Imamura, Minako

AU - Tanaka, Yasushi

AU - Iwata, Minoru

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Maegawa, Hiroshi

AU - Watada, Hirotaka

AU - Tobe, Kazuyuki

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Maeda, Shiro

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Aims: To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods: We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results: Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 % confidence interval = 0.33–0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions: The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.

AB - Aims: To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods: We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results: Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 % confidence interval = 0.33–0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions: The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.

KW - Genetic association studies

KW - Japanese

KW - Single nucleotide polymorphism

KW - Type 2 diabetes mellitus

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