{"entity": "publication", "iuid": "737181efe5d54785b4b4e392d1051968", "timestamp": "2026-09-27T16:15:44.127Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/737181efe5d54785b4b4e392d1051968.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/737181efe5d54785b4b4e392d1051968"}}, "title": "Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis.", "authors": [{"family": "Yu", "given": "Hao", "initials": "H"}, {"family": "Khanshour", "given": "Anas M", "initials": "AM"}, {"family": "Ushiki", "given": "Aki", "initials": "A"}, {"family": "Otomo", "given": "Nao", "initials": "N"}, {"family": "Koike", "given": "Yoshinao", "initials": "Y"}, {"family": "Einarsdottir", "given": "Elisabet", "initials": "E"}, {"family": "Fan", "given": "Yanhui", "initials": "Y"}, {"family": "Antunes", "given": "Lilian", "initials": "L"}, {"family": "Kidane", "given": "Yared H", "initials": "YH"}, {"family": "Cornelia", "given": "Reuel", "initials": "R"}, {"family": "Sheng", "given": "Rory", "initials": "R"}, {"family": "Zhang", "given": "Yichi", "initials": "Y"}, {"family": "Pei", "given": "Jimin", "initials": "J"}, {"family": "Grishin", "given": "Nick V", "initials": "NV"}, {"family": "Evers", "given": "Bret M", "initials": "BM"}, {"family": "Cheung", "given": "Jason Pui Yin", "initials": "JPY"}, {"family": "Herring", "given": "John A", "initials": "JA"}, {"family": "Terao", "given": "Chikashi", "initials": "C"}, {"family": "Song", "given": "You-Qiang", "initials": "YQ"}, {"family": "Gurnett", "given": "Christina A", "initials": "CA"}, {"family": "Gerdhem", "given": "Paul", "initials": "P"}, {"family": "Ikegawa", "given": "Shiro", "initials": "S"}, {"family": "Rios", "given": "Jonathan J", "initials": "JJ"}, {"family": "Ahituv", "given": "Nadav", "initials": "N"}, {"family": "Wise", "given": "Carol A", "initials": "CA", "orcid": "0000-0002-6790-2194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d5371b80b7e45f1b306d0b7680f0bff.json"}}], "type": "preprint", "published": "2023-11-22", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than five-fold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here we sought to define the roles of PAX1 and newly-identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (\u03b11) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); P=7.07e-11, OR=1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (\u03b11) XI protein both localize within the intervertebral disc (IVD)-vertebral junction region encompassing the growth plate, with less collagen (\u03b11) XI detected in Pax1-/- spines compared to wildtype. By genetic targeting we found that wildtype Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, this suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2, or tamoxifen treatment, significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a Pax1-Col11a1-Mmp3 signaling axis in spinal chondrocytes.", "doi": "10.1101/2023.05.26.542293", "pmid": "37292598", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10245954"}, {"db": "pii", "key": "2023.05.26.542293"}], "notes": [], "created": "2026-09-23T14:48:40.641Z", "modified": "2026-09-23T14:48:40.714Z"}