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Most BMD-associated GWAS variants lie in noncoding regions, complicating efforts to identify causal genes and mechanisms. To overcome this variant-to-function challenge, we previously developed STING-seq, a framework integrating biobank-scale GWAS with single-cell CRISPR inhibition (CRISPRi) screening to directly connect noncoding\n                  <jats:italic>cis<\/jats:italic>\n                  -regulatory elements (CREs) to their target genes. Applied to human fetal osteoblast (hFOB) cells across osteogenic differentiation, STING-seq linked 76 CREs to 75 target genes at BMD loci. Arrayed CRISPRi and activation validated key CRE\u2013gene relationships, including long-range enhancers regulating\n                  <jats:italic>CXCL12<\/jats:italic>\n                  (over 500 kb apart). We further uncovered\n                  <jats:italic>trans<\/jats:italic>\n                  -regulatory networks and characterized the\n                  <jats:italic>DAP3<\/jats:italic>\n                  \u2013\n                  <jats:italic>YY1AP1<\/jats:italic>\n                  bidirectional promoter, demonstrating a role for\n                  <jats:italic>DAP3<\/jats:italic>\n                  in mineralization via mitochondrial pathways. Together, these findings provide mechanistic insight into how noncoding GWAS variants shape osteoblast activity and highlight the genes and pathways that mediate genetic effects on BMD.\n                <\/jats:p>","DOI":"10.64898\/2026.02.11.705362","type":"posted-content","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:50:17Z","timestamp":1771311017000},"source":"Crossref","is-referenced-by-count":1,"title":["Identification of target genes and regulatory networks for bone mineral density GWAS loci through systematic targeting and inhibition"],"prefix":"10.64898","author":[{"given":"Mohammadjavad","family":"Kahlani","sequence":"first","affiliation":[{"name":"Donnelly Centre for Cellular and Biomolecular Research, University of Toronto"},{"name":"Department of Molecular Genetics, University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Mesner","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, 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Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Mello","sequence":"additional","affiliation":[{"name":"New York Genome Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Ghatan","sequence":"additional","affiliation":[{"name":"New York Genome Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-8109","authenticated-orcid":false,"given":"Tuuli","family":"Lappalainen","sequence":"additional","affiliation":[{"name":"New York Genome Center"},{"name":"Department of Gene Technology, SciLifeLab, KTH Royal Institute of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-0027","authenticated-orcid":false,"given":"Neville E.","family":"Sanjana","sequence":"additional","affiliation":[{"name":"New York Genome Center"},{"name":"Department of Biology, New York 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