{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:42:02Z","timestamp":1782751322966,"version":"3.54.5"},"reference-count":149,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovenian Research Agency","award":["J3-1759"],"award-info":[{"award-number":["J3-1759"]}]},{"name":"Slovenian Research Agency","award":["J3-4527"],"award-info":[{"award-number":["J3-4527"]}]},{"name":"Slovenian Research Agency","award":["P3-0298"],"award-info":[{"award-number":["P3-0298"]}]},{"name":"Slovenian Research Agency","award":["CA18139"],"award-info":[{"award-number":["CA18139"]}]},{"name":"COST Action","award":["J3-1759"],"award-info":[{"award-number":["J3-1759"]}]},{"name":"COST Action","award":["J3-4527"],"award-info":[{"award-number":["J3-4527"]}]},{"name":"COST Action","award":["P3-0298"],"award-info":[{"award-number":["P3-0298"]}]},{"name":"COST Action","award":["CA18139"],"award-info":[{"award-number":["CA18139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a multifactorial, polygenic disease characterized by reduced bone mineral density (BMD) and increased fracture risk. Genome-wide association studies (GWASs) have identified numerous loci associated with BMD and\/or bone fractures, but functional characterization of these target genes is essential to understand the biological mechanisms underlying osteoporosis. This review focuses on current methodologies and key examples of successful functional studies aimed at evaluating gene function in osteoporosis research. Functional evaluation typically follows a multi-step approach. In silico analyses using omics datasets expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and DNA methylation quantitative trait loci (mQTLs) help prioritize candidate genes and predict relevant biological pathways. In vitro models, including immortalized bone-derived cell lines and primary mesenchymal stem cells (MSCs), are used to explore gene function in osteogenesis. Advanced three-dimensional culture systems provide additional physiological relevance for studying bone-related cellular processes. In situ analyses of patient-derived bone and muscle tissues offer validation in a disease-relevant context, while in vivo studies using mouse and zebrafish models enable comprehensive assessment of gene function in skeletal development and maintenance. Integration of these complementary methodologies helps translate GWAS findings into biological insights and supports the identification of novel therapeutic targets for osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms26157237","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"7237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Recent Advances in Experimental Functional Characterization of GWAS Candidate Genes in Osteoporosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Petra","family":"Malava\u0161i\u010d","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"},{"name":"Department for Laboratory Diagnostics, General Hospital Novo mesto, \u0160mihelska cesta 1, 8000 Novo Mesto, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasna","family":"Lojk","sequence":"additional","affiliation":[{"name":"Clinical Institute of Clinical Chemistry and Biochemistry, University Clinical Center Ljubljana, Njego\u0161eva cesta 4, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija Nika","family":"Lov\u0161in","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janja","family":"Marc","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","article-title":"An overview and management of osteoporosis","volume":"4","author":"Sozen","year":"2017","journal-title":"Eur. 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