Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese
Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese
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DOI：
10.1038/s41467-019-11596-w
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发表时间：
2019-08-15
影响因子：
16.6
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
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作者：
Kou, Ikuyo;Otomo, Nao;Ikegawa, Shiro
青少年特发性脊柱侧凸（AIS）是最常见的小儿脊柱畸形。已经确定了几个AIS易感位点；然而，它们只能解释AIS遗传性的一小部分。为了确定更多的AIS易感位点，我们对包括79211名日本人在内的三项全基因组关联研究进行了荟萃分析。我们确定了20个与AIS显著相关的位点，包括14个以前未报道的位点。这些基因座解释了AIS表型变异的4.6%。我们在14个位点中的7个中发现了21个顺式表达的数量性状位点相关基因。通过女性荟萃分析，我们确定了另外三个重要的基因座。我们还发现AIS与体重指数和尿酸有显著的遗传相关性。细胞型特异性分析显示，AIS在多个细胞型组中具有显著的遗传力富集，提示AIS的病因和发病机制存在异质性。我们的研究结果为AIS的病因和发病机制提供了新的见解。
Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.