{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:22:42Z","timestamp":1779139362097,"version":"3.51.4"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ultimate goal of a genome-wide association study (GWAS) is to translate its discoveries into clinical practice. To explore the clinical use of GWAS findings in the bone field, we conducted a GWAS of dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) traits at 11 skeletal sites, within over 30,000 European individuals from the UK Biobank. A total of 91 unique and independent loci were identified for 11 DXA-derived BMD traits and fractures, including 5 novel loci (harboring the genes ABCA1, CHSY1, CYP24A1, SWAP70, and PAX1) for 6 BMD traits. These loci exhibited evidence of association in both males and females, which could serve as independent replication. We demonstrated that each polygenic risk score (PRS) was independently associated with fracture risk. Although incorporating multiple PRSs (i.e., metaPRS) with clinical risk factors from the Fracture Risk Assessment Tool (FRAX) yielded the highest predictive performance, the improvement was modest in fracture prediction. Additionally, we uncovered genetic correlation and shared polygenicity between head BMD and intracranial aneurysm (IA). Finally, by integrating gene expression and GWAS datasets, we prioritized genes (e.g., ESR1 and SREBF1) encoding druggable human proteins along with their respective inhibitors\/antagonists. In conclusion, this comprehensive investigation reveals a new genetic basis for BMD and its clinical relevance to fracture prediction. More importantly, it suggests that head BMD is genetically correlated with IA. The prioritization of genetically supported targets implies the potential repurposing of drugs [e.g., omega-3 polyunsaturated fatty acid (PUFA) supplements] for the prevention of osteoporosis.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzaf097","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T01:35:32Z","timestamp":1762652132000},"source":"Crossref","is-referenced-by-count":3,"title":["Genome-wide Association Studies of over 30,000 Samples with Bone Mineral Density at Multiple Skeletal Sites and Its Clinical Relevance"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6754-5871","authenticated-orcid":false,"given":"Yu","family":"Qian (\u94b1\u96e8)","sequence":"first","affiliation":[{"name":"Suzhou Laboratory of Precision Health and Data Science, The Second Affiliated Hospital of Soochow University , Suzhou 215004,","place":["China"]},{"name":"Institute of Health Data Science, Soochow University , Suzhou 215001,","place":["China"]},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University , Hangzhou 310030,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6045-038X","authenticated-orcid":false,"given":"Jiangwei","family":"Xia (\u590f\u6c5f\u5a01)","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, National Center for Neurological Disorders, Capital Medical University , Beijing 100053,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-4294","authenticated-orcid":false,"given":"Pingyu","family":"Wang (\u738b\u840d\u7389)","sequence":"additional","affiliation":[{"name":"Binzhou Medical University , Yantai 264003,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-3835","authenticated-orcid":false,"given":"Chao","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University , Shanghai 200433,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8104-4035","authenticated-orcid":false,"given":"Hong-Li","family":"Lin (\u853a\u7ea2\u4e3d)","sequence":"additional","affiliation":[{"name":"School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region 999077,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-2356","authenticated-orcid":false,"given":"Gloria Hoi-Yee","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics, Faculty of 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