@article{78047fba9f004817ad756cc35759b3b4,
title = "A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females",
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.",
author = "{TSRHC Scoliosis Clinical Group} and {Japan Scoliosis Clinical Research Group} and Swarkar Sharma and Douglas Londono and Eckalbar, {Walter L.} and Xiaochong Gao and Dongping Zhang and Kristen Mauldin and Ikuyo Kou and Atsushi Takahashi and Morio Matsumoto and Nobuhiro Kamiya and Murphy, {Karl K.} and Reuel Cornelia and Herring, {John A.} and Dennis Burns and Nadav Ahituv and Shiro Ikegawa and Derek Gordon and Wise, {Carol A.} and L. Karol and K. Rathjen and D. Sucato and J. Birch and C. Johnston and Richards, {B. S.} and T. Mildrant and V. Talwakar and H. Iwinski and R. Muchow and Tassone, {J. C.} and Liu, {X. C.} and R. Shindell and W. Schrader and C. Eberson and A. Lapinsky and R. Loder and J. Davey and Naobumi Hosogane and Yoji Ogura and Yohei Takahashi and Atushi Miyake and Kota Watanabe and Kazuhiro Chiba and Yoshiaki Toyama and Katsuki Kono and Noriaki Kawakami and Taichi Tsuji and Koki Uno and Teppei Suzuki and Manabu Ito and Hideki Sudo",
note = "Funding Information: We thank the patients, their families, other study subjects, and referring physicians for their participation in this research. We also thank J. Rios for critical review of the manuscript, and J. Brandon for administrative assistance. This study was supported by the National Institutes of Health (NICHD award R01HD052973), the TSRHC Research Fund project 867, Crystal Charity Ball, Scoliosis Research Society and the Cain Foundation (to C.A.W.), Scoliosis Research Society (to N.K.) and by NICHD award R01HD059862 and NHGRI awards R01HG005058 and 1R01HG006768 (to N.A.). N.A. is also supported in part by NIGMS award number GM61390, NIDDK award number 1R01DK090382 and NINDS award number 1R01NS079231. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
doi = "10.1038/ncomms7452",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}