Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population

The Hisayama Study

Jun Inaishi, Yoichiro Hirakawa, Momoko Horikoshi, Masato Akiyama, Mayu Higashioka, Masahito Yoshinari, Jun Hata, Naoko Mukai, Yoichiro Kamatani, Yukihide Momozawa, Michiaki Kubo, Toshiharu Ninomiya

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

Context Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain. Objective This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population. Participants The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002. Design The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors. Conclusions These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.

元の言語英語
ページ(範囲)3213-3222
ページ数10
ジャーナルJournal of Clinical Endocrinology and Metabolism
104
発行部数8
DOI
出版物ステータス出版済み - 6 19 2019

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Medical problems
Type 2 Diabetes Mellitus
Population
Hazards
Precision Medicine
Statistics
Proportional Hazards Models
Medicine

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

これを引用

Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population : The Hisayama Study. / Inaishi, Jun; Hirakawa, Yoichiro; Horikoshi, Momoko; Akiyama, Masato; Higashioka, Mayu; Yoshinari, Masahito; Hata, Jun; Mukai, Naoko; Kamatani, Yoichiro; Momozawa, Yukihide; Kubo, Michiaki; Ninomiya, Toshiharu.

:: Journal of Clinical Endocrinology and Metabolism, 巻 104, 番号 8, 19.06.2019, p. 3213-3222.

研究成果: ジャーナルへの寄稿記事

Inaishi, Jun ; Hirakawa, Yoichiro ; Horikoshi, Momoko ; Akiyama, Masato ; Higashioka, Mayu ; Yoshinari, Masahito ; Hata, Jun ; Mukai, Naoko ; Kamatani, Yoichiro ; Momozawa, Yukihide ; Kubo, Michiaki ; Ninomiya, Toshiharu. / Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population : The Hisayama Study. :: Journal of Clinical Endocrinology and Metabolism. 2019 ; 巻 104, 番号 8. pp. 3213-3222.
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title = "Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population: The Hisayama Study",
abstract = "Context Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain. Objective This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population. Participants The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002. Design The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95{\%} CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95{\%} CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95{\%} CI, 0.0284 to 0.0494; cNRI, 0.3565; 95{\%} CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors. Conclusions These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.",
author = "Jun Inaishi and Yoichiro Hirakawa and Momoko Horikoshi and Masato Akiyama and Mayu Higashioka and Masahito Yoshinari and Jun Hata and Naoko Mukai and Yoichiro Kamatani and Yukihide Momozawa and Michiaki Kubo and Toshiharu Ninomiya",
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T1 - Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population

T2 - The Hisayama Study

AU - Inaishi, Jun

AU - Hirakawa, Yoichiro

AU - Horikoshi, Momoko

AU - Akiyama, Masato

AU - Higashioka, Mayu

AU - Yoshinari, Masahito

AU - Hata, Jun

AU - Mukai, Naoko

AU - Kamatani, Yoichiro

AU - Momozawa, Yukihide

AU - Kubo, Michiaki

AU - Ninomiya, Toshiharu

PY - 2019/6/19

Y1 - 2019/6/19

N2 - Context Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain. Objective This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population. Participants The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002. Design The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors. Conclusions These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.

AB - Context Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain. Objective This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population. Participants The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002. Design The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors. Conclusions These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.

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