TY - JOUR
T1 - Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis
T2 - a Mendelian randomization study
AU - Otomo, Nao
AU - Khanshour, Anas M.
AU - Koido, Masaru
AU - Takeda, Kazuki
AU - Momozawa, Yukihide
AU - Kubo, Michiaki
AU - Kamatani, Yoichiro
AU - Herring, John A.
AU - Ogura, Yoji
AU - Takahashi, Yohei
AU - Minami, Shohei
AU - Uno, Koki
AU - Kawakami, Noriaki
AU - Ito, Manabu
AU - Sato, Tatsuya
AU - Watanabe, Kei
AU - Kaito, Takashi
AU - Yanagida, Haruhisa
AU - Taneichi, Hiroshi
AU - Harimaya, Katsumi
AU - Taniguchi, Yuki
AU - Shigematsu, Hideki
AU - Iida, Takahiro
AU - Demura, Satoru
AU - Sugawara, Ryo
AU - Fujita, Nobuyuki
AU - Yagi, Mitsuru
AU - Okada, Eijiro
AU - Hosogane, Naobumi
AU - Kono, Katsuki
AU - Nakamura, Masaya
AU - Chiba, Kazuhiro
AU - Kotani, Toshiaki
AU - Sakuma, Tsuyoshi
AU - Akazawa, Tsutomu
AU - Suzuki, Teppei
AU - Nishida, Kotaro
AU - Kakutani, Kenichiro
AU - Tsuji, Taichi
AU - Sudo, Hideki
AU - Iwata, Akira
AU - Inami, Satoshi
AU - Wise, Carol A.
AU - Kochi, Yuta
AU - Matsumoto, Morio
AU - Ikegawa, Shiro
AU - Watanabe, Kota
AU - Terao, Chikashi
N1 - Publisher Copyright:
Copyright © 2023 Otomo, Khanshour, Koido, Takeda, Momozawa, Kubo, Kamatani, Herring, Ogura, Takahashi, Minami, Uno, Kawakami, Ito, Sato, Watanabe, Kaito, Yanagida, Taneichi, Harimaya, Taniguchi, Shigematsu, Iida, Demura, Sugawara, Fujita, Yagi, Okada, Hosogane, Kono, Nakamura, Chiba, Kotani, Sakuma, Akazawa, Suzuki, Nishida, Kakutani, Tsuji, Sudo, Iwata, Inami, Wise, Kochi, Matsumoto, Ikegawa, Watanabe and Terao.
PY - 2023
Y1 - 2023
N2 - Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.
AB - Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.
KW - Mendelian randomization (MR)
KW - adolescent idiopathic scoliosis
KW - body mass index
KW - genetic study
KW - genome-wide association study
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U2 - 10.3389/fendo.2023.1089414
DO - 10.3389/fendo.2023.1089414
M3 - Article
C2 - 37415668
AN - SCOPUS:85164521540
SN - 1664-2392
VL - 14
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 1089414
ER -