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Original Article
- Genetics
- SLC30A8 Rare Variant Modify Contribution of Common Genetic and Lifestyle Factors toward Type 2 Diabetes Mellitus
- Hye-Mi Jang, Mi Yeong Hwang, Yi Seul Park, Bong-Jo Kim, Young Jin Kim
- Diabetes Metab J. 2026;50(2):385-395. Published online August 13, 2025
- DOI: https://doi.org/10.4093/dmj.2024.0830
- 2,637 View
- 93 Download
- 1 Web of Science
- 2 Crossref
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Abstract
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Supplementary Material
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ePub - Background
This study aimed to investigate the modifying effects of rare genetic variants on the risk of type 2 diabetes mellitus (T2DM) in the context of common genetic and lifestyle factors.
Methods
We conducted a comprehensive analysis of genetic and lifestyle factors associated with T2DM in a cohort of 146,284 Korean individuals. Among them, 4,603 individuals developed T2DM during the follow-up period of up to 17 years. We calculated a polygenic risk score (PRS) for T2DM and identified carriers of the rare allele I349F at SLC30A8. A Healthy Lifestyle Score (HLS) was also derived from physical activity, obesity, smoking, diet, and sodium intake levels. Using Cox proportional hazards models, we analyzed how PRS, HLS, and I349F influenced T2DM incidence.
Results
Results showed that high PRS and poor lifestyle were associated with increased risk. Remarkably, I349F carriers exhibited a lower T2DM prevalence (5.7% compared to 11.7% in non-carriers) and reduced the impact of high PRS from 23.18% to 12.70%. This trend was consistent across different HLS categories, with I349F carriers displaying a lower risk of T2DM.
Conclusion
The integration of common and rare genetic variants with lifestyle factors enhanced T2DM predictability in the Korean population. Our findings highlight the critical role of rare genetic variants in risk assessments and suggest that standard PRS and HLS metrics alone may be inadequate for predicting T2DM risk among carriers of such variants. -
Citations
Citations to this article as recorded by
- Personalised Nutrition in Obesity and Prediabetes: Do Genotypes Matter?
Magdalena Bossowska, Filip Bossowski, Edyta Adamska-Patruno, Katarzyna Maliszewska, Adam Krętowski
Nutrients.2026; 18(5): 815. CrossRef - Differential contributions of cardiovascular health-related lifestyle factors to epigenetic ageing: implications for healthy longevity
Da-eun Lee, Yi Seul Park, Hye-Mi Jang, Bong-Jo Kim, Young Jin Kim, Sung-il Cho, Kyeezu Kim
BMC Medicine.2025;[Epub] CrossRef
- Personalised Nutrition in Obesity and Prediabetes: Do Genotypes Matter?
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