Frontiers in Endocrinology (Jun 2023)

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

  • Nao Otomo,
  • Nao Otomo,
  • Nao Otomo,
  • Anas M. Khanshour,
  • Masaru Koido,
  • Masaru Koido,
  • Kazuki Takeda,
  • Yukihide Momozawa,
  • Michiaki Kubo,
  • Yoichiro Kamatani,
  • Yoichiro Kamatani,
  • John A. Herring,
  • John A. Herring,
  • Yoji Ogura,
  • Yohei Takahashi,
  • Shohei Minami,
  • Koki Uno,
  • Noriaki Kawakami,
  • Manabu Ito,
  • Tatsuya Sato,
  • Kei Watanabe,
  • Takashi Kaito,
  • Haruhisa Yanagida,
  • Hiroshi Taneichi,
  • Katsumi Harimaya,
  • Yuki Taniguchi,
  • Hideki Shigematsu,
  • Takahiro Iida,
  • Takahiro Iida,
  • Satoru Demura,
  • Ryo Sugawara,
  • Nobuyuki Fujita,
  • Nobuyuki Fujita,
  • Mitsuru Yagi,
  • Mitsuru Yagi,
  • Eijiro Okada,
  • Naobumi Hosogane,
  • Naobumi Hosogane,
  • Katsuki Kono,
  • Katsuki Kono,
  • Masaya Nakamura,
  • Kazuhiro Chiba,
  • Kazuhiro Chiba,
  • Toshiaki Kotani,
  • Tsuyoshi Sakuma,
  • Tsutomu Akazawa,
  • Teppei Suzuki,
  • Kotaro Nishida,
  • Kenichiro Kakutani,
  • Taichi Tsuji,
  • Hideki Sudo,
  • Akira Iwata,
  • Satoshi Inami,
  • Carol A. Wise,
  • Carol A. Wise,
  • Carol A. Wise,
  • Yuta Kochi,
  • Morio Matsumoto,
  • Shiro Ikegawa,
  • Kota Watanabe,
  • Chikashi Terao,
  • Chikashi Terao,
  • Chikashi Terao

DOI
https://doi.org/10.3389/fendo.2023.1089414
Journal volume & issue
Vol. 14

Abstract

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IntroductionAdolescent 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 methodsMendelian 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.ResultsSignificant 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.ConclusionsOur 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.

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