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