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However, avascular necrosis (AVN) is a common and debilitating adverse effect, leading to bone death and impacting long\u2010term quality of life. This study aimed to uncover the genetic factors contributing to corticosteroid\u2010induced AVN in a well\u2010characterized cohort of pediatric cancer patients. We conducted a genome\u2010wide association study (GWAS) on 972 patients, including 108 with AVN grade \u22652 and 864 dose\u2010matched controls. The GWAS of 6.4 million genetic markers identified four significant AVN\u2010associated loci (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 5 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ):\n                    <jats:italic>WNT7B<\/jats:italic>\n                    (OR = 9.2; 95% CI, 3.8\u201022.0),\n                    <jats:italic>POGK<\/jats:italic>\n                    (OR = 8.4; 95% CI, 3.6\u201019.5),\n                    <jats:italic>ZNF37A<\/jats:italic>\n                    (OR = 6.0; 95% CI, 2.9\u201012.5), and a synonymous variant in\n                    <jats:italic>FAM240C<\/jats:italic>\n                    (OR = 5.0; 95% CI, 2.6\u20109.5). A multi\u2010marker predictive model combining single nucleotide polymorphisms (SNPs) and clinical factors showed an area under the ROC curve (AUC) of 78.7%, outperforming SNP\u2010only (67.8%) and clinical\u2010only (68.4%) models. The osteogenic processes regulated by\n                    <jats:italic>WNT7B<\/jats:italic>\n                    , part of the Wnt signaling pathway, may contribute to AVN\u2010related disrupted bone development and repair. Similarly,\n                    <jats:italic>POGK<\/jats:italic>\n                    and\n                    <jats:italic>ZNF37A<\/jats:italic>\n                    , both containing the KRAB domain, are hypothesized to affect osteoblast differentiation and skeletal development in AVN. Developing a predictive model for individual susceptibility to corticosteroid\u2010induced AVN will enhance the monitoring and management of corticosteroid use in children with cancer.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70084","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:29:59Z","timestamp":1753446599000},"page":"1844-1854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Four Pharmacogenomic Variants Strongly Linked to Corticosteroid\u2010Induced Avascular Necrosis in Children with Cancer"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-226X","authenticated-orcid":false,"given":"Miguel","family":"Cordova\u2010Delgado","sequence":"first","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics Faculty of Medicine University of British Columbia  Vancouver Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Pharmaceutical Outcomes Programme British Columbia Children's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika N.","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics Faculty of Medicine University of British Columbia  Vancouver Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Department of Medical Genetics Faculty of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrad R.","family":"Rassekh","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Division of Oncology Hematology and Bone Marrow Transplant Department of Pediatrics Faculty of Medicine BC Children's Hospital and University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1167-3721","authenticated-orcid":false,"given":"Catrina M.","family":"Loucks","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics Faculty of Medicine University of British Columbia  Vancouver Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Department of Anesthesiology Pharmacology and Therapeutics Faculty of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Chun","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics Faculty of Medicine University of British Columbia  Vancouver Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Pharmaceutical Outcomes Programme British Columbia Children's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-9415","authenticated-orcid":false,"given":"Edward J.","family":"Raack","sequence":"additional","affiliation":[{"name":"BC Children's Hospital Research Institute  Vancouver Canada"},{"name":"Department of Medical Genetics Faculty of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N.","family":"Trueman","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics Faculty of Medicine University of British Columbia  Vancouver Canada"},{"name":"BC Children's Hospital Research Institute  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J. 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