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

• Published in: Nature communications Vol. 10; no. 1; pp. 3685 - 9
• Main Authors: Kou, Ikuyo, Otomo, Nao, Takeda, Kazuki, Momozawa, Yukihide, Lu, Hsing-Fang, Kubo, Michiaki, Kamatani, Yoichiro, Ogura, Yoji, Takahashi, Yohei, Nakajima, Masahiro, Minami, Shohei, Uno, Koki, Kawakami, Noriaki, Ito, Manabu, Yonezawa, Ikuho, Watanabe, Kei, Kaito, Takashi, Yanagida, Haruhisa, Taneichi, Hiroshi, Harimaya, Katsumi, Taniguchi, Yuki, Shigematsu, Hideki, Iida, Takahiro, Demura, Satoru, Sugawara, Ryo, Fujita, Nobuyuki, Yagi, Mitsuru, Okada, Eijiro, Hosogane, Naobumi, Kono, Katsuki, Nakamura, Masaya, Chiba, Kazuhiro, Kotani, Toshiaki, Sakuma, Tsuyoshi, Akazawa, Tsutomu, Suzuki, Teppei, Nishida, Kotaro, Kakutani, Kenichiro, Tsuji, Taichi, Sudo, Hideki, Iwata, Akira, Sato, Tatsuya, Inami, Satoshi, Matsumoto, Morio, Terao, Chikashi, Watanabe, Kota, Ikegawa, Shiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-08-2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38/109; 38/71; 38/77; 45/43; 631/208/205/2138; 631/443/63; 692/420/2489/144; Adolescent; Asian Continental Ancestry Group - genetics; Body mass; Body Mass Index; Body size; Etiology; Female; Gene expression; Gene mapping; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Heritability; Heterogeneity; Humanities and Social Sciences; Humans; Japan; Male; multidisciplinary; Pathogenesis; Phenotypic variations; Quantitative trait loci; Quantitative Trait Loci - genetics; Science; Science (multidisciplinary); Scoliosis; Scoliosis - genetics; Sex Factors; Uric acid; Uric Acid - metabolism; Japan
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11596-w

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.
Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.