增强子
基因座(遗传学)
全基因组关联研究
单核苷酸多态性
遗传学
生物
斑马鱼
等位基因
遗传关联
性二态性
SNP公司
转录因子
基因
基因型
内分泌学
作者
Swarkar Sharma,Douglas Londoño,Walter L. Eckalbar,Xiaochong Gao,Dongping Zhang,Kristen Mauldin,Ikuyo Kou,Atsushi Takahashi,Morio Matsumoto,Nobuhiro Kamiya,Karl K. Murphy,Reuel Cornelia,John A. Herring,Dennis K. Burns,Nadav Ahituv,Shiro Ikegawa,Derek Gordon,Carol A. Wise
摘要
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.
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