Jun Inaishi1, Yoichiro Hirakawa1,2, Momoko Horikoshi3, Masato Akiyama4,5, Mayu Higashioka1,6, Masahito Yoshinari1,2, Jun Hata1,2, Naoko Mukai1,2, Yoichiro Kamatani4, Yukihide Momozawa7, Michiaki Kubo8, Toshiharu Ninomiya1. 1. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 4. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 5. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Department of Diabetes and Molecular Genetics, Graduate School of Medicine, Ehime University, Ehime, Japan. 7. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical, Sciences, Yokohama, Japan. 8. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
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.
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.
Authors: América Liliana Miranda-Lora; Jenny Vilchis-Gil; Daniel B Juárez-Comboni; Miguel Cruz; Miguel Klünder-Klünder Journal: Front Endocrinol (Lausanne) Date: 2021-03-12 Impact factor: 5.555