{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:09:37Z","timestamp":1793210977695,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT","award":["NRF-2021R1F1A1045417"],"award-info":[{"award-number":["NRF-2021R1F1A1045417"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Genom. Med."],"DOI":"10.1038\/s41525-025-00520-5","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:19:31Z","timestamp":1760098771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Whole genome sequencing in adolescent idiopathic scoliosis cohort implicates multiple biological pathways"],"prefix":"10.1038","volume":"10","author":[{"given":"Islam Oguz","family":"Tuncay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Kyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxhela","family":"Gustafson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonsuh","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawoon","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June-Young","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonchul","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangmoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Shazand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"520_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.2106\/00004623-197860020-00005","volume":"60","author":"EJ Rogala","year":"1978","unstructured":"Rogala, E. J., Drummond, D. S. & Gurr, J. Scoliosis: incidence and natural history. A prospective epidemiological study. J. Bone Jt. Surg. 60, 173\u2013176 (1978).","journal-title":"J. Bone Jt. Surg."},{"key":"520_CR2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1748-7161-1-2","volume":"1","author":"MA Asher","year":"2006","unstructured":"Asher, M. A. & Burton, D. C. Adolescent idiopathic scoliosis: natural history and long term treatment effects. Scoliosis 1, 2 (2006).","journal-title":"Scoliosis"},{"key":"520_CR3","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.2106\/00004623-199710000-00006","volume":"79","author":"PN Soucacos","year":"1997","unstructured":"Soucacos, P. N., Soucacos, P. K., Zacharis, K. C., Beris, A. E. & Xenakis, T. A. School-screening for scoliosis. A prospective epidemiological study in northwestern and central Greece. J. Bone Jt. Surg. 79, 1498\u20131503 (1997).","journal-title":"J. Bone Jt. Surg."},{"key":"520_CR4","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/S0140-6736(08)60658-3","volume":"371","author":"SL Weinstein","year":"2008","unstructured":"Weinstein, S. L., Dolan, L. A., Cheng, J. C., Danielsson, A. & Morcuende, J. A. Adolescent idiopathic scoliosis. Lancet 371, 1527\u20131537 (2008).","journal-title":"Lancet"},{"key":"520_CR5","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jama.2017.11669","volume":"319","author":"J Dunn","year":"2018","unstructured":"Dunn, J. et al. Screening for adolescent idiopathic scoliosis: evidence report and systematic review for the US preventive services task force. JAMA J. Am. Med. Assoc. 319, 173 (2018).","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"520_CR6","doi-asserted-by":"publisher","unstructured":"Barton, C. B. & Weinstein, S. L. Adolescent idiopathic scoliosis: natural history. In Pathogenesis of Idiopathic Scoliosis, 27\u201350 (Springer, 2018). https:\/\/doi.org\/10.1007\/978-4-431-56541-3_2.","DOI":"10.1007\/978-4-431-56541-3_2"},{"key":"520_CR7","doi-asserted-by":"publisher","first-page":"115563","DOI":"10.1016\/j.bone.2020.115563","volume":"140","author":"G P\u00e9rez-Machado","year":"2020","unstructured":"P\u00e9rez-Machado, G. et al. From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis. Bone 140, 115563 (2020).","journal-title":"Bone"},{"key":"520_CR8","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1530\/EOR-22-0026","volume":"7","author":"T Cheng","year":"2022","unstructured":"Cheng, T., Einarsdottir, E., Kere, J. & Gerdhem, P. Idiopathic scoliosis: a systematic review and meta-analysis of heritability. EFORT Open Rev. 7, 414\u2013421 (2022).","journal-title":"EFORT Open Rev."},{"key":"520_CR9","doi-asserted-by":"publisher","first-page":"284","DOI":"10.2106\/JBJS.16.00459","volume":"99","author":"K Watanabe","year":"2017","unstructured":"Watanabe, K. et al. Physical activities and lifestyle factors related to adolescent idiopathic scoliosis. J. Bone Jt. Surg. 99, 284\u2013294 (2017).","journal-title":"J. Bone Jt. Surg."},{"key":"520_CR10","doi-asserted-by":"publisher","first-page":"922","DOI":"10.3390\/genes12060922","volume":"12","author":"EA Terhune","year":"2021","unstructured":"Terhune, E. A. et al. Whole exome sequencing of 23 multigeneration idiopathic scoliosis families reveals enrichments in cytoskeletal variants, suggests highly polygenic disease. Genes12, 922 (2021).","journal-title":"Genes"},{"key":"520_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-019-2402-x","volume":"20","author":"C Xia","year":"2019","unstructured":"Xia, C. et al. Rare variant of HSPG2 is not involved in the development of adolescent idiopathic scoliosis: evidence from a large-scale replication study. BMC Musculoskelet. Disord. 20, 24 (2019).","journal-title":"BMC Musculoskelet. Disord."},{"key":"520_CR12","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/jor.21322","volume":"29","author":"Y Takahashi","year":"2011","unstructured":"Takahashi, Y. et al. Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes. J. Orthop. Res. 29, 834\u2013837 (2011).","journal-title":"J. Orthop. Res."},{"key":"520_CR13","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1093\/hmg\/ddq571","volume":"20","author":"S Sharma","year":"2011","unstructured":"Sharma, S. et al. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum. Mol. Genet 20, 1456\u20131466 (2011).","journal-title":"Hum. Mol. Genet"},{"key":"520_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7452","volume":"6","author":"S Sharma","year":"2015","unstructured":"Sharma, S. et al. A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nat. Commun. 6, 6452 (2015).","journal-title":"Nat. Commun."},{"key":"520_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9355","volume":"6","author":"Z Zhu","year":"2015","unstructured":"Zhu, Z. et al. Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat. Commun. 6, 8355 (2015).","journal-title":"Nat. Commun."},{"key":"520_CR16","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1093\/hmg\/ddx045","volume":"26","author":"Z Zhu","year":"2017","unstructured":"Zhu, Z. et al. Genome-wide association study identifies novel susceptible loci and highlights Wnt\/beta-catenin pathway in the development of adolescent idiopathic scoliosis. Hum. Mol. Genet 26, 1577\u20131583 (2017).","journal-title":"Hum. Mol. Genet"},{"key":"520_CR17","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/ng.974","volume":"43","author":"Y Takahashi","year":"2011","unstructured":"Takahashi, Y. et al. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat. Genet 43, 1237\u20131240 (2011).","journal-title":"Nat. Genet"},{"key":"520_CR18","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1097\/BRS.0000000000002111","volume":"42","author":"S Liu","year":"2017","unstructured":"Liu, S. et al. Genetic polymorphism of LBX1 is associated with adolescent idiopathic scoliosis in Northern Chinese Han population. Spine 42, 1125\u20131129 (2017).","journal-title":"Spine"},{"key":"520_CR19","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1111\/jcmm.13486","volume":"22","author":"G Liu","year":"2018","unstructured":"Liu, G. et al. Genetic polymorphisms of GPR126 are functionally associated with PUMC classifications of adolescent idiopathic scoliosis in a Northern Han population. J. Cell Mol. Med 22, 1964\u20131971 (2018).","journal-title":"J. Cell Mol. Med"},{"key":"520_CR20","doi-asserted-by":"crossref","unstructured":"Liu, G. et al. Genetic polymorphisms of PAX1 are functionally associated with different PUMC types of adolescent idiopathic scoliosis in a northern Chinese Han population. Gene 688, 215\u2013220 (2019).","DOI":"10.1016\/j.gene.2018.12.013"},{"key":"520_CR21","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1097\/BRS.0000000000002866","volume":"44","author":"GC-W Man","year":"2019","unstructured":"Man, G. C.-W. et al. Replication study for the association of GWAS-associated Loci with adolescent idiopathic scoliosis susceptibility and curve progression in a Chinese population. Spine 44, 464\u2013471 (2019).","journal-title":"Spine"},{"key":"520_CR22","doi-asserted-by":"publisher","first-page":"E1098","DOI":"10.1097\/BRS.0000000000002123","volume":"42","author":"X Qin","year":"2017","unstructured":"Qin, X. et al. Genetic variant of GPR126 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Spine42, E1098\u2013E1103 (2017).","journal-title":"Spine"},{"key":"520_CR23","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/BRS.0000000000002475","volume":"43","author":"L Xu","year":"2018","unstructured":"Xu, L. et al. Genetic variant of PAX1 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Spine 43, 492\u2013496 (2018).","journal-title":"Spine"},{"key":"520_CR24","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s00438-017-1315-3","volume":"292","author":"L Xu","year":"2017","unstructured":"Xu, L. et al. Genetic variant of BNC2 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Mol. Genet. Genomics 292, 789\u2013794 (2017).","journal-title":"Mol. Genet. Genomics"},{"key":"520_CR25","doi-asserted-by":"publisher","first-page":"E618","DOI":"10.1097\/BRS.0000000000003857","volume":"46","author":"Z Wu","year":"2021","unstructured":"Wu, Z. et al. Genetic variants of CHD7 are associated with adolescent idiopathic scoliosis. Spine 46, E618\u2013E624 (2021).","journal-title":"Spine"},{"key":"520_CR26","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/BRS.0000000000003700","volume":"46","author":"Y Li","year":"2021","unstructured":"Li, Y. et al. Genetic variant of TBX1 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population. Spine 46, 17\u201321 (2021).","journal-title":"Spine"},{"key":"520_CR27","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.spinee.2015.05.013","volume":"15","author":"A Grauers","year":"2015","unstructured":"Grauers, A. et al. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis. Spine J. 15, 2239\u20132246 (2015).","journal-title":"Spine J."},{"key":"520_CR28","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1097\/BRS.0000000000002280","volume":"43","author":"D Nada","year":"2018","unstructured":"Nada, D., Julien, C., Samuels, M. E. & Moreau, A. A replication study for association of LBX1 locus with adolescent idiopathic scoliosis in French\u2013Canadian population. Spine 43, 172\u2013178 (2018).","journal-title":"Spine"},{"key":"520_CR29","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1126\/science.add4867","volume":"376","author":"E Pennisi","year":"2022","unstructured":"Pennisi, E. & Upstart, D. N. A. sequencers could be a \u2018game changer\u2019. Science 376, 1257\u20131258 (2022).","journal-title":"Science"},{"key":"520_CR30","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk, D. et al. The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638\u2013D646 (2023).","journal-title":"Nucleic Acids Res."},{"key":"520_CR31","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1097\/01241398-200211000-00017","volume":"22","author":"E Morava","year":"2002","unstructured":"Morava, E., Lacassie, Y., King, A., Illes, T. & Marble, M. Scoliosis in velo-cardio-facial syndrome. J. Pediatr. Orthop. 22, 780\u2013783 (2002).","journal-title":"J. Pediatr. Orthop."},{"key":"520_CR32","doi-asserted-by":"crossref","unstructured":"Du, Q., de la Morena, M. T. & van Oers, N. S. C. The genetics and epigenetics of 22q11.2 deletion syndrome. Front. Genet. 10, 1365 (2020).","DOI":"10.3389\/fgene.2019.01365"},{"key":"520_CR33","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13052-022-01267-w","volume":"48","author":"LC Wiel","year":"2022","unstructured":"Wiel, L. C., Bruno, I., Barbi, E. & Sirchia, F. From Wolf-Hirschhorn syndrome to NSD2 haploinsufficiency: a shifting paradigm through the description of a new case and a review of the literature. Ital. J. Pediatr. 48, 72 (2022).","journal-title":"Ital. J. Pediatr."},{"key":"520_CR34","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1002\/ar.24086","volume":"303","author":"SR Lamand\u00e9","year":"2020","unstructured":"Lamand\u00e9, S. R. & Bateman, J. F. Genetic disorders of the extracellular matrix. Anat. Rec. 303, 1527\u20131542 (2020).","journal-title":"Anat. Rec."},{"key":"520_CR35","doi-asserted-by":"publisher","first-page":"5271","DOI":"10.1093\/hmg\/ddu224","volume":"23","author":"JG Buchan","year":"2014","unstructured":"Buchan, J. G. et al. Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Hum. Mol. Genet 23, 5271\u20135282 (2014).","journal-title":"Hum. Mol. Genet"},{"key":"520_CR36","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1534\/g3.114.015669","volume":"5","author":"EE Baschal","year":"2015","unstructured":"Baschal, E. E. et al. Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis. G3 Genes Genomes Genet. 5, 167\u2013174 (2015).","journal-title":"G3 Genes Genomes Genet."},{"key":"520_CR37","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3109\/ort.1965.36.suppl-81.01","volume":"36","author":"J-E Michelsson","year":"1965","unstructured":"Michelsson, J.-E. The development of spinal deformity in experimental scoliosis. Acta Orthop. Scand. 36, 3\u201391 (1965).","journal-title":"Acta Orthop. Scand."},{"key":"520_CR38","doi-asserted-by":"publisher","first-page":"611","DOI":"10.2106\/00004623-196244040-00002","volume":"44","author":"DL Stilwell","year":"1962","unstructured":"Stilwell, D. L. Structural deformities of vertebrae: bone adaptation and modeling in experimental scoliosis and kyphosis. J. Bone Jt. Surg. 44, 611\u2013634 (1962).","journal-title":"J. Bone Jt. Surg."},{"key":"520_CR39","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3109\/03008200903215590","volume":"51","author":"S Wang","year":"2010","unstructured":"Wang, S. et al. Expression of Runx2 and type X collagen in vertebral growth plate of patients with adolescent idiopathic scoliosis. Connect Tissue Res. 51, 188\u2013196 (2010).","journal-title":"Connect Tissue Res."},{"key":"520_CR40","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1097\/00007632-200405010-00012","volume":"29","author":"J Cheung","year":"2004","unstructured":"Cheung, J. et al. The relation between electromyography and growth velocity of the spine in the evaluation of curve progression in idiopathic scoliosis. Spine 29, 1011\u20131016 (2004).","journal-title":"Spine"},{"key":"520_CR41","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.jelekin.2014.05.014","volume":"24","author":"N Farahpour","year":"2014","unstructured":"Farahpour, N., Ghasemi, S., Allard, P. & Saba, M. S. Electromyographic responses of erector spinae and lower limb\u2019s muscles to dynamic postural perturbations in patients with adolescent idiopathic scoliosis. J. Electromyogr. Kinesiol. 24, 645\u2013651 (2014).","journal-title":"J. Electromyogr. Kinesiol."},{"key":"520_CR42","doi-asserted-by":"publisher","first-page":"3146","DOI":"10.1007\/s00586-016-4628-8","volume":"25","author":"I Stetkarova","year":"2016","unstructured":"Stetkarova, I. et al. Electrophysiological and histological changes of paraspinal muscles in adolescent idiopathic scoliosis. Eur. Spine J. 25, 3146\u20133153 (2016).","journal-title":"Eur. Spine J."},{"key":"520_CR43","doi-asserted-by":"publisher","first-page":"e72802","DOI":"10.1371\/journal.pone.0072802","volume":"8","author":"A Miyake","year":"2013","unstructured":"Miyake, A. et al. Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3. PLoS One 8, e72802 (2013).","journal-title":"PLoS One"},{"key":"520_CR44","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.matbio.2020.09.003","volume":"94","author":"M Tsingas","year":"2020","unstructured":"Tsingas, M. et al. Sox9 deletion causes severe intervertebral disc degeneration characterized by apoptosis, matrix remodeling, and compartment-specific transcriptomic changes. Matrix Biol. 94, 110\u2013133 (2020).","journal-title":"Matrix Biol."},{"key":"520_CR45","doi-asserted-by":"crossref","unstructured":"G\u00fcven, A. et al. Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex. Elife 9, 49808 (2020).","DOI":"10.7554\/eLife.49808"},{"key":"520_CR46","first-page":"146","volume":"04","author":"M Villa","year":"2015","unstructured":"Villa, M. Genes associated with adolescent idiopathic scoliosis: a review. Hereditary Genet. 04, 146 (2015).","journal-title":"Hereditary Genet."},{"key":"520_CR47","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.ejmg.2008.09.002","volume":"51","author":"M Blyth","year":"2008","unstructured":"Blyth, M., Huang, S., Maloney, V., Crolla, J. A. & Karen Temple, I. A 2.3\u2009Mb deletion of 17q24.2\u2013q24.3 associated with \u2018Carney Complex plus\u2019. Eur. J. Med. Genet. 51, 672\u2013678 (2008).","journal-title":"Eur. J. Med. Genet."},{"key":"520_CR48","doi-asserted-by":"publisher","first-page":"26499","DOI":"10.1074\/jbc.M500375200","volume":"280","author":"E Mizuhara","year":"2005","unstructured":"Mizuhara, E. et al. MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface. J. Biol. Chem. 280, 26499\u201326507 (2005).","journal-title":"J. Biol. Chem."},{"key":"520_CR49","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ajhg.2015.06.012","volume":"97","author":"Y Ogura","year":"2015","unstructured":"Ogura, Y. et al. A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am. J. Hum. Genet. 97, 337\u2013342 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"520_CR50","doi-asserted-by":"publisher","first-page":"3986","DOI":"10.1093\/hmg\/ddy306","volume":"27","author":"AM Khanshour","year":"2018","unstructured":"Khanshour, A. M. et al. Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci. Hum. Mol. Genet. 27, 3986\u20133998 (2018).","journal-title":"Hum. Mol. Genet."},{"key":"520_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33063-9","volume":"13","author":"M Bobowski-Gerard","year":"2022","unstructured":"Bobowski-Gerard, M. et al. Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis. Nat. Commun. 13, 5324 (2022).","journal-title":"Nat. Commun."},{"key":"520_CR52","doi-asserted-by":"publisher","first-page":"e202301984","DOI":"10.26508\/lsa.202301984","volume":"6","author":"A Orang","year":"2023","unstructured":"Orang, A. et al. Basonuclin-2 regulates extracellular matrix production and degradation. Life Sci. Alliance 6, e202301984 (2023).","journal-title":"Life Sci. Alliance"},{"key":"520_CR53","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41525-022-00284-2","volume":"7","author":"IO Tuncay","year":"2022","unstructured":"Tuncay, I. O. et al. Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants. NPJ Genom. Med. 7, 13 (2022).","journal-title":"NPJ Genom. Med."},{"key":"520_CR54","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41525-022-00288-y","volume":"7","author":"R Lesurf","year":"2022","unstructured":"Lesurf, R. et al. Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy. NPJ Genom. Med. 7, 18 (2022).","journal-title":"NPJ Genom. Med."},{"key":"520_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-247","volume":"15","author":"AM Meynert","year":"2014","unstructured":"Meynert, A. M., Ansari, M., FitzPatrick, D. R. & Taylor, M. S. Variant detection sensitivity and biases in whole genome and exome sequencing. BMC Bioinforma. 15, 247 (2014).","journal-title":"BMC Bioinforma."},{"key":"520_CR56","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1073\/pnas.1418631112","volume":"112","author":"A Belkadi","year":"2015","unstructured":"Belkadi, A. et al. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc. Natl. Acad. Sci. 112, 5473\u20135478 (2015).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"520_CR57","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/BF00301052","volume":"2","author":"CJ Goldberg","year":"1993","unstructured":"Goldberg, C. J., Dowling, F. E. & Fogarty, E. E. Adolescent idiopathic scoliosis: is rising growth rate the triggering factor in progression?. Eur. Spine J. 2, 29\u201336 (1993).","journal-title":"Eur. Spine J."},{"key":"520_CR58","first-page":"193","volume":"89","author":"JP Horne","year":"2014","unstructured":"Horne, J. P., Flannery, R. & Usman, S. Adolescent idiopathic scoliosis: diagnosis and management. Am. Fam. Phys.89, 193\u2013198 (2014).","journal-title":"Am. Fam. Phys."},{"key":"520_CR59","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature 526, 68\u201374 (2015).","journal-title":"Nature"},{"key":"520_CR60","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434\u2013443 (2020).","journal-title":"Nature"},{"key":"520_CR61","doi-asserted-by":"publisher","first-page":"D840","DOI":"10.1093\/nar\/gkw971","volume":"45","author":"KJ Karczewski","year":"2017","unstructured":"Karczewski, K. J. et al. The ExAC browser: displaying reference data information from over 60 000 exomes. Nucleic Acids Res. 45, D840\u2013D845 (2017).","journal-title":"Nucleic Acids Res."},{"key":"520_CR62","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013424 (2015).","journal-title":"Genet. Med."},{"key":"520_CR63","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ng.2639","volume":"45","author":"I Kou","year":"2013","unstructured":"Kou, I. et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat. Genet. 45, 676\u2013679 (2013).","journal-title":"Nat. Genet."},{"key":"520_CR64","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1136\/jmedgenet-2015-103684","volume":"53","author":"W Li","year":"2016","unstructured":"Li, W. et al. AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis. J. Med. Genet. 53, 488\u2013493 (2016).","journal-title":"J. Med. Genet."},{"key":"520_CR65","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1086\/513571","volume":"80","author":"X Gao","year":"2007","unstructured":"Gao, X. et al. CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis. Am. J. Hum. Genet. 80, 957\u2013965 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"520_CR66","doi-asserted-by":"publisher","first-page":"E1432","DOI":"10.1097\/BRS.0b013e3182a51781","volume":"38","author":"MK Tilley","year":"2013","unstructured":"Tilley, M. K. et al. CHD7 gene polymorphisms and familial idiopathic scoliosis. Spine 38, E1432\u2013E1436 (2013).","journal-title":"Spine"},{"key":"520_CR67","unstructured":"Yu, H. et al. Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis. Elife 12, 89762v3 (2024)."},{"key":"520_CR68","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1093\/hmg\/ddad117","volume":"32","author":"D Rebello","year":"2023","unstructured":"Rebello, D. et al. COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis. Hum. Mol. Genet. 32, 2913\u20132928 (2023).","journal-title":"Hum. Mol. Genet."},{"key":"520_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-16620-6","volume":"12","author":"D Nada","year":"2022","unstructured":"Nada, D. et al. Identification of FAT3 as a new candidate gene for adolescent idiopathic scoliosis. Sci. Rep. 12, 12298 (2022).","journal-title":"Sci. Rep."},{"key":"520_CR70","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/humu.24162","volume":"42","author":"EA Terhune","year":"2021","unstructured":"Terhune, E. A. et al. Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish. Hum. Mutat. 42, 392\u2013407 (2021).","journal-title":"Hum. Mutat."},{"key":"520_CR71","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1016\/j.spinee.2019.06.014","volume":"19","author":"W Jennings","year":"2019","unstructured":"Jennings, W. et al. Paraspinal muscle ladybird homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study. Spine J. 19, 1911\u20131916 (2019).","journal-title":"Spine J."},{"key":"520_CR72","doi-asserted-by":"publisher","first-page":"e0213269","DOI":"10.1371\/journal.pone.0213269","volume":"14","author":"A Hassan","year":"2019","unstructured":"Hassan, A. et al. Adolescent idiopathic scoliosis associated POC5 mutation impairs cell cycle, cilia length and centrosome protein interactions. PLoS One 14, e0213269 (2019).","journal-title":"PLoS One"},{"key":"520_CR73","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"520_CR74","doi-asserted-by":"crossref","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","DOI":"10.1186\/s13742-015-0047-8"},{"key":"520_CR75","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"520_CR76","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner, M. et al. Gene ontology: tool for the unification of biology. Nat. Genet 25, 25\u201329 (2000).","journal-title":"Nat. Genet"},{"key":"520_CR77","doi-asserted-by":"publisher","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","volume":"49","author":"S Carbon","year":"2021","unstructured":"Carbon, S. et al. The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res. 49, D325\u2013D334 (2021).","journal-title":"Nucleic Acids Res."},{"key":"520_CR78","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90\u2013W97 (2016).","journal-title":"Nucleic Acids Res."}],"container-title":["npj Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41525-025-00520-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41525-025-00520-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41525-025-00520-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:18Z","timestamp":1760104998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41525-025-00520-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["520"],"URL":"https:\/\/doi.org\/10.1038\/s41525-025-00520-5","relation":{},"ISSN":["2056-7944"],"issn-type":[{"value":"2056-7944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]},"assertion":[{"value":"27 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}