PUBLICATION

A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females

Authors
Sharma, S., Londono, D., Eckalbar, W.L., Gao, X., Zhang, D., Mauldin, K., Kou, I., Takahashi, A., Matsumoto, M., Kamiya, N., Murphy, K.K., Cornelia, R., TSRHC Scoliosis Clinical Group, Japan Scoliosis Clinical Research Group, Herring, J.A., Burns, D., Ahituv, N., Ikegawa, S., Gordon, D., Wise, C.A.
ID
ZDB-PUB-150319-5
Date
2015
Source
Nature communications   6: 6452 (Journal)
Registered Authors
Ahituv, Nadav, Murphy, Karl
Keywords
none
MeSH Terms
  • Phenotype
  • Linkage Disequilibrium
  • Female
  • Genotype
  • Animals
  • Chromosome Mapping
  • Risk Factors
  • Paired Box Transcription Factors/genetics*
  • Paired Box Transcription Factors/physiology
  • Humans
  • United States
  • Japan
  • Zebrafish
  • Sex Factors
  • Cohort Studies
  • Genetic Predisposition to Disease*
  • Mutation
  • Polymorphism, Single Nucleotide
  • Alleles
  • Genome-Wide Association Study
  • Enhancer Elements, Genetic*
  • Scoliosis/genetics*
  • Male
  • Sequence Analysis, DNA
(all 24)
PubMed
25784220 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
No images available
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
Sharma, S., Londono, D., Eckalbar, W.L., Gao, X., Zhang, D., Mauldin, K., Kou, I., Takahashi, A., Matsumoto, M., Kamiya, N., Murphy, K.K., Cornelia, R., TSRHC Scoliosis Clinical Group, Japan Scoliosis Clinical Research Group, Herring, J.A., Burns, D., Ahituv, N., Ikegawa, S., Gordon, D., Wise, C.A. (2015) A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nature communications. 6:6452.