TY - JOUR
T1 - A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis
AU - Japan Scoliosis Clinical Research Group (JSCRG)
AU - Takeda, Kazuki
AU - Kou, Ikuyo
AU - Otomo, Nao
AU - Grauers, Anna
AU - Fan, Yan Hui
AU - Ogura, Yoji
AU - Takahashi, Yohei
AU - Momozawa, Yukihide
AU - Einarsdottir, Elisabet
AU - Kere, Juha
AU - Kawakami, Noriaki
AU - Tsuji, Taichi
AU - Uno, Koki
AU - Suzuki, Teppei
AU - Ito, Manabu
AU - Minami, Shohei
AU - Kotani, Toshiaki
AU - Sakuma, Tsuyoshi
AU - Yanagida, Haruhisa
AU - Taneichi, Hiroshi
AU - Yonezawa, Ikuho
AU - Sudo, Hideki
AU - Chiba, Kazuhiro
AU - Hosogane, Naobumi
AU - Nishida, Kotaro
AU - Kakutani, Kenichiro
AU - Akazawa, Tsutomu
AU - Kaito, Takashi
AU - Watanabe, Kei
AU - Harimaya, Katsumi
AU - Taniguchi, Yuki
AU - Shigematsu, Hideki
AU - Demura, Satoru
AU - Iida, Takahiro
AU - Kono, Katsuki
AU - Okada, Eijiro
AU - Fujita, Nobuyuki
AU - Yagi, Mitsuru
AU - Matsumoto, Morio
AU - Qiu, Yong
AU - Song, You Qiang
AU - Gerdhem, Paul
AU - Watanabe, Kota
AU - Ikegawa, Shiro
N1 - Funding Information:
Acknowledgements We are grateful to the individuals who participated in this study. We thank all participating subjects and clinical staff at collaborating institutes. We specially thank Y. Takahashi, T. Oguma and the members of Laboratory for Genotyping Development for technical assistance. This work was supported by Japan Agency for Medical Research and Development (AMED) (contract no. 18ek0109212h0002 to SI), Japan Orthopaedics and Traumatology Foundation (to KT and NO), Hong Kong Health and Medical Research Fund (HMRF No. 04152256) (to Y-QS) and the Swedish Research Council (No. K-2013-52X-22198-01-3) (to AG and PG).
Publisher Copyright:
© 2019, The Author(s) under exclusive licence to The Japan Society of Human Genetics.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10 −13 ; odds ratio = 1.36, 95% confidence interval = 1.25−1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.
AB - Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10 −13 ; odds ratio = 1.36, 95% confidence interval = 1.25−1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.
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U2 - 10.1038/s10038-019-0575-7
DO - 10.1038/s10038-019-0575-7
M3 - Article
C2 - 30787423
AN - SCOPUS:85061838312
SN - 1434-5161
VL - 64
SP - 493
EP - 498
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 5
ER -