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

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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.

Original languageEnglish
Pages (from-to)3213-3222
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume104
Issue number8
DOIs
Publication statusPublished - 19-06-2019

All Science Journal Classification (ASJC) codes

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

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    Inaishi, J., Hirakawa, Y., Horikoshi, M., Akiyama, M., Higashioka, M., Yoshinari, M., Hata, J., Mukai, N., Kamatani, Y., Momozawa, Y., Kubo, M., & Ninomiya, T. (2019). Association between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population: The Hisayama Study. Journal of Clinical Endocrinology and Metabolism, 104(8), 3213-3222. https://doi.org/10.1210/jc.2018-01782