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PubMed · 41992540

Polygenic risk scores and lifestyle factors predicting new onset of type 2 diabetes in the Japanese general population.

Megumi Oshima·Akinori Hara·Tadashi Toyama·Atsushi Asayama·Taihei Yamaguchi·Atsushi Tajima·Hiromasa Tsujiguchi·Masahiro Ozawa·Takehiro Sato·Kazuyoshi Hosomichi·Takayuki Kannon·Yumie Takeshita·Toshinari Takamura·Norihiko Sakai·Miho Shimizu·Hiroyuki Nakamura·Takashi Wada·Yasunori Iwata
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Abstract

PURPOSE: This study investigated the association of polygenic risk scores (PRS) and lifestyle factors with type 2 diabetes mellitus development in Japanese populations and evaluated whether PRS can improve diabetes risk prediction beyond traditional risk factors. METHODS: We conducted a cross-sectional and a longitudinal study using the Shika resident cohort (n = 895) and the Toshiba worker cohort (n = 7019), respectively. Participants were categorized into low, intermediate, and high genetic risk groups using PRS constructed with genome-wide association study data from East Asian populations. We defined diabetes based on hemoglobin A1c, fasting blood glucose, self-reported diagnosis, or medication use. The associations of PRS and lifestyle factors with diabetes development were analyzed using multivariate logistic regression and Cox proportional hazards models. RESULTS: Higher PRS were associated with increased diabetes risk in both cohorts (resident cohort: odds ratio 4.51, 95% CI 2.53-8.04; worker cohort: hazard ratio 1.50, 95% CI 1.23-1.83 for high vs low PRS), which remained consistent across age, body mass index, and comorbidities. Regular exercise, absence of hypertension, and absence of dyslipidemia were associated with lower diabetes risk, particularly in the high PRS group. The addition of PRS to conventional prediction models improved the discrimination of diabetes risk. MAIN CONCLUSION: PRS are associated with diabetes risk in Japanese general populations, independent of traditional risk factors. Nonetheless, healthy lifestyle habits may reduce diabetes risk even among genetically susceptible individuals, which support the utility of PRS for personalized diabetes risk assessment and prevention strategies.

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AdultAgedFemaleHumansMaleMiddle AgedCross-Sectional StudiesDiabetes Mellitus, Type 2Genetic Risk ScoreGenome-Wide Association StudyJapanLife StyleLongitudinal StudiesPrognosisRisk FactorsEast Asian Peoplelifestylepolygenic risk scoretype 2 diabetesJournal Article

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Megumi Oshima, Akinori Hara, Tadashi Toyama, Atsushi Asayama, Taihei Yamaguchi, Atsushi Tajima, Hiromasa Tsujiguchi, Masahiro Ozawa, Takehiro Sato, Kazuyoshi Hosomichi, Takayuki Kannon, Yumie Takeshita, Toshinari Takamura, Norihiko Sakai, Miho Shimizu, Hiroyuki Nakamura, Takashi Wada, Yasunori Iwata. 2026-09-16. Polygenic risk scores and lifestyle factors predicting new onset of type 2 diabetes in the Japanese general population.. https://doi.org/10.1210/clinem%2Fdgag171

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