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A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females.
Sharma, Swarkar; Londono, Douglas; Eckalbar, Walter L; Gao, Xiaochong; Zhang, Dongping; Mauldin, Kristen; Kou, Ikuyo; Takahashi, Atsushi; Matsumoto, Morio; Kamiya, Nobuhiro; Murphy, Karl K; Cornelia, Reuel; Herring, John A; Burns, Dennis; Ahituv, Nadav; Ikegawa, Shiro; Gordon, Derek; Wise, Carol A.
Affiliation
  • Sharma S; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Londono D; Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854, USA.
  • Eckalbar WL; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
  • Gao X; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Zhang D; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Mauldin K; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Kou I; Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo 108-8639, Japan.
  • Takahashi A; Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
  • Matsumoto M; Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo 108-8345, Japan.
  • Kamiya N; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Murphy KK; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
  • Cornelia R; Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA.
  • Herring JA; 1] Department of Orthopaedics, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA [2] Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
  • Burns D; Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
  • Ahituv N; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
  • Ikegawa S; Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo 108-8639, Japan.
  • Gordon D; Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854, USA.
  • Wise CA; 1] Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Research Department, Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA [2] Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA [3] McDermott Cente
Nat Commun ; 6: 6452, 2015 Mar 18.
Article in En | MEDLINE | ID: mdl-25784220
ABSTRACT
Idiopathic scoliosis (IS) is a common paediatric musculoskeletal disease that displays a strong female bias. By performing a genome-wide association study (GWAS) of 3,102 individuals, we identify significant associations with 20p11.22 SNPs for females (P=6.89 × 10(-9)) but not males (P=0.71). This association with IS is also found in independent female cohorts from the United States of America and Japan (overall P=2.15 × 10(-10), OR=1.30 (rs6137473)). Unexpectedly, the 20p11.22 IS risk alleles were previously associated with protection from early-onset alopecia, another sexually dimorphic condition. The 174-kb associated locus is distal to PAX1, which encodes paired box 1, a transcription factor involved in spine development. We identify a sequence in the associated locus with enhancer activity in zebrafish somitic muscle and spinal cord, an activity that is abolished by IS-associated SNPs. We thus identify a sexually dimorphic IS susceptibility locus, and propose the first functionally defined candidate mutations in an enhancer that may regulate expression in specific spinal cells.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scoliosis / Enhancer Elements, Genetic / Genetic Predisposition to Disease / Paired Box Transcription Factors Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Country/Region as subject: America do norte / Asia Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2015 Document type: Article Affiliation country: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scoliosis / Enhancer Elements, Genetic / Genetic Predisposition to Disease / Paired Box Transcription Factors Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Country/Region as subject: America do norte / Asia Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2015 Document type: Article Affiliation country: Estados Unidos