ArticlePLoS medicine2020
Development of a polygenic risk score to improve screening for fracture risk: A genetic risk prediction study.
Article in PLoS medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Low Circulating Valine Associate With High Risk of Hip Fractures.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- Using a Polygenic Score to Predict the Risk of Developing Primary Osteoporosis.International journal of molecular sciences · 2022Pooled it
- Impact of Genetics on Endocrine Manifestations of Cystic Fibrosis.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026Review
- Osteoporosis genetic risk prediction using bone mineral density polygenic scores in Japanese: TMM CommCohort study.Journal of human genetics · 2026Article
- Validation of fracture-derived polygenic scores with FRAX for fracture risk prediction in postmenopausal women.Archives of osteoporosis · 2026Article
- Prognostic Association of Handgrip-Defined Probable or Possible Sarcopenia Status and Polygenic Risk with 10-Year Fracture Incidence among Black, Hispanic, and White Women: A Women's Health Initiative Study.medRxiv : the preprint server for health sciences · 2026Article
- The SINTER study: a recall-by-genotype design with multidimensional musculoskeletal phenotyping across internal-medicine outpatient clinics.European journal of epidemiology · 2026Article
- Advanced Bayesian BMD-Derived Genome-Wide Polygenic Scores Enhance Clinical FRAX-Based Fracture Risk Prediction in Postmenopausal Women.Calcified tissue international · 2026Article
- Low Trauma Fractures in People With HIV: Longitudinal Time Trends in the Swiss HIV Cohort Study, 2009-2022.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Article
- Genomics in Health and Biomedicine.Advances in experimental medicine and biology · 2026Review
- Association of a polygenic risk score with low trauma fractures in people with HIV - The swiss HIV cohort study.PloS one · 2026Article
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- The gSOS polygenic score is associated with bone density and fracture risk in childhood.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Polygenic Risk Score as a Predictor of Bone Fracture or Osteoporosis in Prostate Cancer Patients Receiving Androgen Deprivation Therapy.Cancer medicine · 2025Article
- Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men.The Journal of clinical endocrinology and metabolism · 2025Article
- Bayesian Genome-wide Polygenic Score Integration with FRAX for Enhanced Fracture Risk Prediction in Postmenopausal Women.medRxiv : the preprint server for health sciences · 2025Article
- Serum creatinine, genetic susceptibility, and the risk of osteoporosis and fracture: a prospective cohort study from the UK Biobank.Frontiers in endocrinology · 2025Article
- Genetic Risk Scores for the Clinical Rheumatologist.Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases · 2025Review
- Genome-wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia.British journal of haematology · 2024Article
Corrections and comments
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Authors and funding
26 authors at 14 institutions in 6 countries.
Funding
Abstract
backgroundSince screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be screened by removing individuals at low genetic risk. We therefore tested whether a polygenic risk score for heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-can identify low-risk individuals who can safely be excluded from a fracture risk screening program. METHODS AND
findingsA polygenic risk score for SOS was trained and selected in 2 separate subsets of UK Biobank (comprising 341,449 and 5,335 individuals). The top-performing prediction model was termed "gSOS", and its utility in fracture risk screening was tested in 5 validation cohorts using the National Osteoporosis Guideline Group clinical guidelines (N = 10,522 eligible participants). All individuals were genome-wide genotyped and had measured fracture risk factors. Across the 5 cohorts, the average age ranged from 57 to 75 years, and 54% of studied individuals were women. The main outcomes were the sensitivity and specificity to correctly identify individuals requiring treatment with and without genetic prescreening. The reference standard was a bone mineral density (BMD)-based Fracture Risk Assessment Tool (FRAX) score. The secondary outcomes were the proportions of the screened population requiring clinical-risk-factor-based FRAX (CRF-FRAX) screening and BMD-based FRAX (BMD-FRAX) screening. gSOS was strongly correlated with measured SOS (r2 = 23.2%, 95% CI 22.7% to 23.7%). Without genetic prescreening, guideline recommendations achieved a sensitivity and specificity for correct treatment assignment of 99.6% and 97.1%, respectively, in the validation cohorts. However, 81% of the population required CRF-FRAX tests, and 37% required BMD-FRAX tests to achieve this accuracy. Using gSOS in prescreening and limiting further assessment to those with a low gSOS resulted in small changes to the sensitivity and specificity (93.4% and 98.5%, respectively), but the proportions of individuals requiring CRF-FRAX tests and BMD-FRAX tests were reduced by 37% and 41%, respectively. Study limitations include a reliance on cohorts of predominantly European ethnicity and use of a proxy of fracture risk.
conclusionsOur results suggest that the use of a polygenic risk score in fracture risk screening could decrease the number of individuals requiring screening tests, including BMD measurement, while maintaining a high sensitivity and specificity to identify individuals who should be recommended an intervention.
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