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

TSRHC Scoliosis Clinical Group, Japan Scoliosis Clinical Research Group

研究成果: Article

67 引用 (Scopus)

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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.

元の言語English
記事番号6452
ジャーナルNature communications
6
DOI
出版物ステータスPublished - 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    TSRHC Scoliosis Clinical Group, & Japan Scoliosis Clinical Research Group (2015). A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nature communications, 6, [6452]. https://doi.org/10.1038/ncomms7452