Puntuaciones de riesgo poligénico (PRS): una herramienta en la predicción de enfermedades y la medicina personalizada / Polygenic risk scores (PRS) - A tool for disease prediction and personalized medicine

En la última década, la genómica y la secuenciación de alto rendimiento han revolucionado la comprensión de las enfermedades complejas. las puntuaciones de riesgo poligénico (PRS) surgen como una prometedora herramienta para predecir enfermedades y personalizar tratamientos. Sin embargo, su implementación requiere confirmar la utilidad real y plantea importantes desafíos éticos y de privacidad. Las PRS se utilizan para identificar individuos de alto riesgo y guiar tratamientos personalizados. Su potencial es evidente en enfermedades como el cáncer o la osteoporosis, donde mejoran la estratificación de riesgo y permiten seleccionar tratamientos más efectivos. Sin embargo, las PRS tienen múltiples limitaciones, incluyendo la falta de precisión individual, la variabilidad en diferentes poblaciones y la incapacidad de considerar la influencia de los factores ambientales. La interpretación clínica y las implicaciones éticas, legales y sociales (ELSI) representan cuestiones muy relevantes en este campo. En el futuro, presumiblemente las PRS mejorarán su precisión predictiva, con la combinación de factores clínicos de riesgo y la adaptación a poblaciones de diversas etnias. Consecuentemente, se prevé que las PRS desempeñen un papel central en la medicina personalizada. (AU)

Over the past decade, genomics and high-throughput sequencing have revolutionized our understanding of complex diseases. Polygenic risk scores (PRS) have emerged as a promising tool for predicting diseases and personalizing treatments. However, their implementation requires confirmation of real utility, which raises significant ethical and privacy challenges. PRS are used to identify high-risk individuals and guide personalized treatments. Their potential is evident in diseases such as cancer or osteoporosis, where they improve risk stratification and enable the selection of more effective treatments. However, PRS have multiple limitations, including lack of individual accuracy, variability among different populations, and the inability to account for the impact of environmental factors. Clinical interpretation and ethical, legal, and social implications (ELSI) are highly relevant issues in this field. In the future, PRS are expected to improve their predictive accuracy by combining clinical risk factors and adapting to populations of various ethnicities. Consequently, PRS are expected to play a central role in personalized medicine. (AU)

Polygenic risk of bone fractures in Spanish women with osteoporosis / Riesgo poligénico de fracturas óseas en mujeres españolas con osteoporosis

Background: osteoporosis is a highly polygenic trait characterized by low bone mineral density (BMD) and/or fragility frac-tures. Over the past decade, polygenic risk scores (PRS) are an emerging tool to try to predict the risk of complex disorderswith a genetic component.Objective: to analyze the capacity of different PRSs to predict osteoporosis in the Spanish population.Material and methods: our dataset consisted of two differentiated groups. The first group included osteoporosis casesdiagnosed and treated at the Marques de Valdecilla University Hospital (n = 304; 293 women) while the second groupconsisted of people from the overall Spanish population (n = 3199; 1458 women). Four previously generated PRSs werecompared with generalized linear models.Results: the osteoporosis group showed a significantly higher genetic risk compared to the control group in 3 PRSs (PRS-1p = 1e-7; PRS-2 p = 1.87e-15; PRS-3 p = 0.1477; PRS-4 p = 8.98e-9). In addition, in these PRSs, the individuals in the upperquartile of risk had a significantly higher risk of osteoporosis, compared to those individuals in the other quartiles (PRS-1OR, 1.83; PRS-2 OR, 2.11; PRS-3 OR, 0.96; PRS-4 OR, 1.72).Conclusions: in summary, the application of PRSs shows significant differences between the overall Spanish populationand patients with osteoporosis, which is suggestive of its utility within strategies for the identification of subjects at riskbased on clinical-genetic criteria.(AU)

Exposure to particulate matter: Direct and indirect role in the COVID-19 pandemic.

Knowing the transmission factors and the natural environment that favor the spread of a viral infection is crucial to stop outbreaks and develop effective preventive strategies. This work aims to evaluate the role of Particulate Matter (PM) in the COVID-19 pandemic, focusing especially on that of PM as a vector for SARS-CoV-2. Exposure to PM has been related to new cases and to the clinical severity of people infected by SARS-CoV-2, which can be explained by the oxidative stress and the inflammatory response generated by these particles when entering the respiratory system, as well as by the role of PM in the expression of ACE-2 in respiratory cells in human hosts. In addition, different authors have detected SARS-CoV-2 RNA in PM sampled both in outdoor and indoor environments. The results of various studies lead to the hypothesis that the aerosols emitted by an infected person could be deposited in other suspended particles, sometimes of natural but especially of anthropogenic origin, that form the basal PM. However, the viability of the virus in PM has not yet been demonstrated. Should PM be confirmed as a vector of transmission, prevention strategies ought to be adapted, and PM sampling in outdoor environments could become an indicator of viral load in a specific area.

Epigenetic related changes on air quality.

The exposure to airborne particulate matter (PM) increases the risk of developing human diseases. Epigenetic mechanisms have been related to environmental exposures and human diseases. The present review is focused on current available studies, which show the relationship between epigenetic marks, exposure to air pollution and human's health. Air contaminants involved in epigenetic changes have been related to different specific mechanisms (DNA methylation, post-translational histone modifications and non-coding RNA transcripts), which are described in separate sections. Several studies describe how these epigenetic mechanisms are influenced by environmental factors including air pollution. This interaction between PM and epigenetic factors results in an altered profile of these marks, in both, globally and locus specific. Following this connection, specific epigenetic marks can be used as biomarkers, as well as, to find new therapeutic targets. For this purpose, some significant characteristics have been highlighted, such as, the spatiotemporal specificity of these marks, the relevance of the collected tissue and the specific changes stability. Air pollution has been related to a higher mortality rate due to non-accidental deaths. This exposure to particulate matter induces changes to the epigenome, which are increasing the susceptibility of human diseases. In conclusion, as several epigenetic change mechanisms remain unclear yet, further analyses derived from PM exposure must be performed to find new targets and disease biomarkers.