期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7452
关键词
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资金
- National Institutes of Health (NICHD) [R01HD052973]
- TSRHC Research Fund project [867]
- Crystal Charity Ball
- Scoliosis Research Society
- Cain Foundation
- NICHD [R01HD059862]
- NHGRI [R01HG005058, 1R01HG006768]
- NIGMS [GM61390]
- NIDDK [1R01DK090382]
- NINDS [1R01NS079231]
- Grants-in-Aid for Scientific Research [24390357] Funding Source: KAKEN
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 x 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 x 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.
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