Background: Parkinson’s disease (PD) is a neurodegenerative disorder, and literature suggests that genetics and lifestyle/environmental factors may play a key role in the triggering of the disease. This study aimed to evaluate the predictive performance of a 12-Single Nucleotide Polymorphisms (SNPs) polygenic risk score (PRS) in combination with already established PD-environmental/lifestyle factors. Methods: Genotypic and lifestyle/environmental data on 235 PD-patients and 464 controls were obtained from a previous study carried out in the Cypriot population. A PRS was calculated for each individual. Univariate logistic-regression analysis was used to assess the association of PRS and each risk factor with PD-status. Stepwise-regression analysis was used to select the best predictive model for PD combining genetic and lifestyle/environmental factors. Results: The 12-SNPs PRS was significantly increased in PD-cases compared to controls. Furthermore, univariate analyses showed that age, head injury, family history, depression, and Body Mass Index (BMI) were significantly associated with PD-status. Stepwise-regression suggested that a model which includes PRS and seven other independent lifestyle/environmental factors is the most predictive of PD in our population. Conclusions: These results suggest an association between both genetic and environmental factors and PD, and highlight the potential for the use of PRS in combination with the classical risk factors for risk prediction of PD.

The PRS combines multiplicatively the effects of common low-risk single nucleotide polymorphisms (SNPs) and has the potential to be used for the estimation of an individual’s risk for a trait or disease. PRS has been successfully implemented for the prediction of breast cancer risk. The combination of PRS with classical breast cancer risk factors provides a more comprehensive risk estimation and could, thus, improve risk stratification and personalized preventative strategies. In this study, we assessed the predictive performance of the combined effect of PRS₁₅ with classical breast-cancer risk factors in Cypriot women using 1109 cases and 1177 controls from the MASTOS study. The PRS₁₅ was significantly associated with an increased breast cancer risk in Cypriot women OR (95% CI) 1.66 (1.25–2.19). The integrated risk model obtained an AUC (95% CI) 0.70 (0.67–0.72) and had the ability to stratify women according to their disease status at the extreme deciles. These results provide evidence that the combination of PRS with classical risk factors may be used in the future for the stratification of Cypriot women based on their disease risk, and support its potential clinical utility for targeted preventative actions and population screening.

Iron overload-driven liver fibrosis is a major concern in β-thalassaemia patients, but non-invasive or minimally invasive biomarkers for fibrosis staging remain limited. This study evaluated five plasma microRNAs (let-7a, miR-21, miR-29a, miR-34a, and miR-122) as potential markers for distinguishing liver fibrosis stages in β-thalassaemia. Plasma samples from 40 patients with fibrosis stages F0–F1 to F4 were analysed using RT-qPCR, normalised against the arithmetic mean of reference miRNAs miR-16 and miR-221. Expression levels of candidate miRNAs showed no statistically significant variation across stages, and logistic regression and ROC analyses revealed fair discriminatory performance for individual miRNAs and their combinations in selected stage comparisons. Notably, while for the discrimination of different fibrosis stages all five candidate miRNAs tested showed fair area-under-the-curve values between 0.7 and 0.8 individually and up to 0.917 in combination, none of these findings reached statistical significance. These results suggest that while the selected set of miRNAs reflects liver injury, its performance for precise fibrosis staging in β-thalassaemia is limited. A key cause for the low discriminatory power of these miRNAs may be the overall change of the blood miRNA transcriptome in haemoglobinopathies. The results indicate the need for validation in larger cohorts based on larger miRNA panels or the use of alternative source materials to improve diagnostic performance.