ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2025
The gSOS polygenic score is associated with bone density and fracture risk in childhood.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The polygenic risk score genetic quantitative ultrasound speed of sound (gSOS) was developed using machine learning algorithms in adults of European ancestry and associates with reduced odds of fracture in adults. We aimed to determine if gSOS was associated with bone health in children. Two observational studies of children were evaluated: (1) children enrolled in the Bone Mineral Density in Childhood Study (BMDCS) with genetic data (N = 1727) and (2) children with genetic data for research at the Children's Hospital of Philadelphia (CHOP; N = 10 301). Genetic variants were used to calculate gSOS and genetic ancestry. For the BMDCS, puberty stage, dietary calcium, physical activity, and fracture accumulation (none or ≥1 fracture) were self-reported, height and weight were measured and BMI calculated. Areal BMD (aBMD) of the lumbar spine, hip, radius, and whole body were assessed by DXA and expressed as Z-scores. The CHOP study paired genetic data with documentation of fracture in the electronic health record (EHR). Genetic quantitative ultrasound speed of sound associated with higher aBMD Z-scores across 7 skeletal sites [eg, a 1 SD increase in gSOS associated with 0.17 (95% CI: 0.10-0.24) higher LS aBMD Z-score]. These associations were consistent for males and females, age, puberty stage, and lifestyle factors, and most consistent among children of European genetic ancestry. A 1 SD increase in gSOS associated with 24% reduced likelihood of self-reported fracture in the BMDCS (OR = 0.76, 95% CI: 0.66, 0.88) and a 12% reduced likelihood of a recorded fracture in the CHOP EHR (OR = 0.88; 95% CI: 0.82, 0.95). No sex or genetic ancestry differences were found. A higher gSOS score associated with higher aBMD at multiple skeletal sites and reduced odds of fracture in two independent pediatric samples. This genetic tool may have clinical utility to help enhance bone health in early life and protect against fracture across the lifespan.
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