{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:45:18Z","timestamp":1792003518290,"version":"4.4.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":203,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05453"],"award-info":[{"award-number":["16H05453"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02931"],"award-info":[{"award-number":["18H02931"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05453"],"award-info":[{"award-number":["16H05453"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02931"],"award-info":[{"award-number":["18H02931"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p\u00a0=\u00a03.5\u2009\u00d7\u200910\u221240 with area under the receiver-operating characteristic [AUROC]\u00a0=\u00a00.674, sensitivity\u00a0=\u00a00.644, and specificity\u00a0=\u00a00.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p\u00a0=\u00a01.4\u2009\u00d7\u200910\u221210) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC\u00a0=\u00a00.722, net reclassification improvement [NRI] 0.505\u2009\u00b1\u20090.054, p\u00a0=\u00a01.6\u2009\u00d7\u200910\u22128), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg\u00a0=\u00a00.6, p\u00a0=\u00a03.0\u2009\u00d7\u200910\u22124). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4324","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:11:03Z","timestamp":1624407063000},"page":"1481-1491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use"],"prefix":"10.1093","volume":"36","author":[{"given":"Nao","family":"Otomo","sequence":"first","affiliation":[{"name":"Laboratory for Statistical and Translational Genetics Center for Integrative Medical Sciences, RIKEN Yokohama Japan"},{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"},{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-5188","authenticated-orcid":false,"given":"Hsing-Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Taipei Medical University Taipei Taiwan"},{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-0666","authenticated-orcid":false,"given":"Masaru","family":"Koido","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science The University of Tokyo Tokyo Japan"},{"name":"Laboratory for Statistical and Translational Genetics Center for Integrative Medical Sciences, RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuyo","family":"Kou","sequence":"additional","affiliation":[{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"},{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihide","family":"Momozawa","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development Center for Integrative Medical Sciences, RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Kubo","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development Center for Integrative Medical Sciences, RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kamatani","sequence":"additional","affiliation":[{"name":"Laboratory of Complex Trait Genomics, Graduate School of Frontier Science The University of Tokyo Tokyo Japan"},{"name":"Laboratory for Statistical and Translational Genetics Center for Integrative Medical Sciences, RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seirei Sakura Citizen Hospital Sakura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Uno","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery National Hospital Organization, Kobe Medical Center Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Meijo Hospital Nagoya 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhisa","family":"Yanagida","sequence":"additional","affiliation":[{"name":"Department of Orthopedic & Spine Surgery Fukuoka Children's Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Taneichi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Dokkyo Medical University School of Medicine Mibu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Harimaya","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Kyushu University Beppu Hospital Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine The University of Tokyo Tokyo 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Fujita Health University Toyoake Japan"},{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Yagi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eijiro","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naobumi","family":"Hosogane","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery National Defense Medical College Tokorozawa Japan"},{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuki","family":"Kono","sequence":"additional","affiliation":[{"name":"Kono Orthopaedic Clinic Tokyo Japan"},{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery National Defense Medical College Tokorozawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Kotani","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seirei Sakura Citizen Hospital Sakura 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Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inami","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Dokkyo Medical University School of Medicine Mibu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Kochi","sequence":"additional","affiliation":[{"name":"Department of Genomic Function and Diversity, Medical Research Institute Tokyo Medical and Dental and University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chiao","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Biomarkers and Biotech Drugs Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Department of Pharmacy Taipei Medical University-Wangfang Hospital Taipei Taiwan"},{"name":"Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy Taipei Medical University Taipei Taiwan"},{"name":"Department of Clinical Pharmacy Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morio","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Ikegawa","sequence":"additional","affiliation":[{"name":"Laboratory for Bone and Joint Diseases Center for Integrative Medical Sciences, RIKEN Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-4095","authenticated-orcid":false,"given":"Chikashi","family":"Terao","sequence":"additional","affiliation":[{"name":"Department of Applied Genetics, The School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan"},{"name":"Clinical Research Center Shizuoka General Hospital Shizuoka Japan"},{"name":"Laboratory for Statistical and Translational Genetics Center for Integrative Medical Sciences, RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"issue":"1","key":"2024012713455768800_jbmr4324-bib-0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11420-009-9136-5","article-title":"The Hospital for Special Surgery 1955 to 1972: T. Campbell Thompson serves as sixth surgeon-in-chief 1955-1963 followed by Robert Lee Patterson, Jr. the seventh surgeon-in-chief 1963-1972","volume":"6","author":"Levine","year":"2010","journal-title":"HSS J."},{"issue":"7","key":"2024012713455768800_jbmr4324-bib-0002","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1148\/rg.307105061","article-title":"Scoliosis imaging: what radiologists should know","volume":"30","author":"Kim","year":"2010","journal-title":"Radiographics."},{"issue":"24","key":"2024012713455768800_jbmr4324-bib-0003","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1097\/00007632-199912150-00006","article-title":"Natural history","volume":"24","author":"Weinstein","year":"1999","journal-title":"Spine (Phila Pa 1976)"},{"issue":"1","key":"2024012713455768800_jbmr4324-bib-0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00776-010-0009-z","article-title":"A 5-year epidemiological study on the prevalence rate of idiopathic scoliosis in Tokyo: school screening of more than 250,000 children","volume":"16","author":"Ueno","year":"2011","journal-title":"J Orthop Sci."},{"issue":"14","key":"2024012713455768800_jbmr4324-bib-0005","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1097\/00007632-200207150-00012","article-title":"Patient and parental perception of adolescent idiopathic scoliosis before and after surgery in comparison with surface and radiographic measurements","volume":"27","author":"Pratt","year":"2002","journal-title":"Spine (Phila Pa 1976)"},{"issue":"5","key":"2024012713455768800_jbmr4324-bib-0006","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00007632-198905000-00001","article-title":"The psychological impact of idiopathic scoliosis on the adolescent female. A preliminary multi-center study","volume":"14","author":"Kahanovitz","year":"1989","journal-title":"Spine (Phila Pa 1976)."},{"issue":"5","key":"2024012713455768800_jbmr4324-bib-0007","doi-asserted-by":"crossref","first-page":"702","DOI":"10.2106\/00004623-198163050-00003","article-title":"Idiopathic scoliosis: long-term follow-up and prognosis in untreated patients","volume":"63","author":"Weinstein","year":"1981","journal-title":"J Bone Joint Surg Am."},{"issue":"1","key":"2024012713455768800_jbmr4324-bib-0008","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13013-014-0021-8","article-title":"A health economic evaluation of screening and treatment in patients with adolescent idiopathic scoliosis","volume":"9","author":"Adobor","year":"2014","journal-title":"Scoliosis."},{"issue":"15","key":"2024012713455768800_jbmr4324-bib-0009","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2106\/JBJS.15.01313","article-title":"The effect of the Risser stage on bracing outcome in adolescent idiopathic scoliosis","volume":"98","author":"Karol","year":"2016","journal-title":"J Bone Joint Surg Am"},{"issue":"16","key":"2024012713455768800_jbmr4324-bib-0010","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1056\/NEJMoa1307337","article-title":"Effects of bracing in adolescents with idiopathic scoliosis","volume":"369","author":"Weinstein","year":"2013","journal-title":"N Engl J Med"},{"issue":"5","key":"2024012713455768800_jbmr4324-bib-0011","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/ajmg.a.33145","article-title":"Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah","volume":"152a","author":"Ward","year":"2010","journal-title":"Am J Med Genet A"},{"issue":"6","key":"2024012713455768800_jbmr4324-bib-0012","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1469-8749.1973.tb04919.x","article-title":"Genetic aspects of idiopathic scoliosis","volume":"15","author":"Wynne-Davies","year":"1973","journal-title":"Dev Med Child Neurol."},{"issue":"4","key":"2024012713455768800_jbmr4324-bib-0013","doi-asserted-by":"crossref","first-page":"284","DOI":"10.2106\/JBJS.16.00459","article-title":"Physical activities and lifestyle factors related to adolescent idiopathic scoliosis","volume":"99","author":"Watanabe","year":"2017","journal-title":"J Bone Joint Surg Am"},{"issue":"17","key":"2024012713455768800_jbmr4324-bib-0014","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1097\/00007632-199709010-00014","article-title":"Scoliosis in twins. 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