A PRS FOR TYPE 2 DIABETES

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Type 2 Diabetes (T2D) is a chronic condition characterized by high blood sugar levels, which can lead to serious health complications. The importance of early detection and prevention cannot be overstated, as it helps in managing the disease and reducing the risk of complications. According to recent statistics, millions of people are affected by T2D globally, making it a significant public health concern. 

T2D is a multifactorial disease, meaning its development is influenced by both genetic and environmental factors. This complex interplay makes predicting and managing the disease challenging. While lifestyle factors like diet and exercise play a crucial role, genetic predispositions significantly influence an individual's risk of developing T2D. 

Lifestyle and environmental factors are critical in the development of T2D. These include obesity, lack of physical activity, poor diet, and smoking. Such factors are modifiable, offering opportunities for intervention and prevention strategies to reduce the risk of T2D. 

Genetic predisposition plays a crucial role in T2D. MODY, a hereditary form of diabetes, typically manifests in adolescence or early adulthood and is caused by mutations in single genes that significantly impact pancreatic beta-cell function. Unlike the more common polygenic T2D, MODY results from specific gene mutations, such as those in HNF1A, GCK, and HNF4A, leading to varying clinical presentations and treatment responses. However, the contribution of polygenic factors, where multiple genes affect the risk, is increasingly recognized as significant. 

Polygenic Risk Scores (PRS) have emerged as a powerful tool in assessing the risk of T2D. PRS aggregates multiple genetic variants to calculate an individual's predisposition to T2D, offering a more nuanced understanding than single-gene analyses. Integrating PRS into clinical practice can enhance the early detection and personalized management of T2D. Studies have shown that PRS, in combination with traditional risk factors, can significantly improve the prediction of T2D, highlighting the clinical utility of PRS in managing this complex disease (Padilla-Martínez et al., 2020), (Merino et al., 2022), (Ge et al., 2021). In addition, PRS for differentiating type 1 diabetes (T1D) and type 2 diabetes (T2D) achieved reasonably high predictive capacity. A study using PRS for T1D pointed out that PRS is an important addition to correctly classifying young adults with diabetes. The PRS was highly discriminative of T1D and T2D in young individuals and identified patients with diabetes who will require insulin treatment (Oram et al., 2016). It has also been shown that the risk of developing T2D at an earlier age, progressing to an insulin-dependent stage, and having a low response to glucose-lowering drugs has been linked to a high T2D PRS (Jiang et al., 2020). 

The integration of PRS in T2D risk assessment represents a significant advancement in personalized medicine. By considering the unique genetic makeup of individuals, PRS enables more accurate predictions of T2D risk, facilitating early interventions and tailored management strategies.