[HTML][HTML] Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

I Kou, N Otomo, K Takeda, Y Momozawa, HF Lu… - Nature …, 2019 - nature.com
I Kou, N Otomo, K Takeda, Y Momozawa, HF Lu, M Kubo, Y Kamatani, Y Ogura
Nature communications, 2019nature.com
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 …
Abstract
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.
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