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Article: Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci

TitleGenome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci
Authors
Keywordsimmunoprecipitation
cartilage
child development
chondrocytes
chondrogenesis
Issue Date2018
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2018, v. 27 n. 22, p. 3986-3998 How to Cite?
AbstractAdolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/275683
ISSN
2017 Impact Factor: 4.902
2015 SCImago Journal Rankings: 4.288
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorKhanshour, AM-
dc.contributor.authorKou, I-
dc.contributor.authorFan, Y-
dc.contributor.authorEinarsdottir, E-
dc.contributor.authorMakki, N-
dc.contributor.authorKidane, YH-
dc.contributor.authorKere, J-
dc.contributor.authorGrauers, A-
dc.contributor.authorJohnson, TA-
dc.contributor.authorParia, N-
dc.contributor.authorPatel, C-
dc.contributor.authorSinghania, R-
dc.contributor.authorKamiya, N-
dc.contributor.authorTakeda, K-
dc.contributor.authorOtomo, N-
dc.contributor.authorWatanabe, K-
dc.contributor.authorLuk, KDK-
dc.contributor.authorCheung, KMC-
dc.contributor.authorHerring, JA-
dc.contributor.authorRios, JJ-
dc.contributor.authorAhituv, N-
dc.contributor.authorGerdhem, P-
dc.contributor.authorGurnett, CA-
dc.contributor.authorSong, Y-
dc.contributor.authorIkegawa, S-
dc.contributor.authorWise, CA-
dc.date.accessioned2019-09-10T02:47:32Z-
dc.date.available2019-09-10T02:47:32Z-
dc.date.issued2018-
dc.identifier.citationHuman Molecular Genetics, 2018, v. 27 n. 22, p. 3986-3998-
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/275683-
dc.description.abstractAdolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/-
dc.relation.ispartofHuman Molecular Genetics-
dc.rightsPre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here].-
dc.subjectimmunoprecipitation-
dc.subjectcartilage-
dc.subjectchild development-
dc.subjectchondrocytes-
dc.subjectchondrogenesis-
dc.titleGenome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci-
dc.typeArticle-
dc.identifier.emailCheung, KMC: cheungmc@hku.hk-
dc.identifier.emailSong, Y: songy@hku.hk-
dc.identifier.authorityLuk, KDK=rp00333-
dc.identifier.authorityCheung, KMC=rp00387-
dc.identifier.authoritySong, Y=rp00488-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/hmg/ddy306-
dc.identifier.pmid30395268-
dc.identifier.pmcidPMC6488972-
dc.identifier.scopuseid_2-s2.0-85056288930-
dc.identifier.hkuros303698-
dc.identifier.volume27-
dc.identifier.issue22-
dc.identifier.spage3986-
dc.identifier.epage3998-
dc.publisher.placeUnited Kingdom-

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