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

ABSTRACT

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)