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

Nao Otomo, Anas M Khanshour, Masaru Koido, Kazuki Takeda, Yukihide Momozawa, Michiaki Kubo, Yoichiro Kamatani, 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, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Masaya Nakamura, 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, Yuta Kochi, Morio Matsumoto, Shiro Ikegawa, Kota Watanabe, Chikashi Terao

Journal: Frontiers in endocrinology 2023;14():1089414

PMID: 37415668

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Plain Language Summary

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity influenced by both genetic predisposition and environmental factors. Previous studies have found an association between low body mass index (BMI) and IAS. This Mendelian randomisation study analysed the large genome-wide association studies of AIS and association with BMI. The research findings demonstrate a causal association between the genetic variants contributing to low BMI and the occurrence of IAS. A reverse Mendelian randomisation showed that the occurrence of AIS had no causal effect on low BMI. Healthcare professionals can use the findings of this research for early detection of IAS. However, further robust large studies are required to investigate the causal association of low BMI on the onset of IAS in different ethnic populations.

Abstract

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), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10), 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.

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.

Address: Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.; Center for Translational Research, Scottish Rite for Children, Dallas, TX, United States.; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.; Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.; Laboratory of Complex Trait Genomics, Graduate School of Frontier Science, The University of Tokyo, Tokyo, Japan.; Department of Orthopaedic Surgery , Scottish Rite for Children, Dallas, TX, United States.; Department of Orthopaedic Surgery and Pediatric, University of Texas Southwestern Medical Center, Dallas, TX, United States.; Department of Orthopaedic Surgery, Seirei Sakura Citizen Hospital, Sakura, Japan.; Department of Orthopaedic Surgery, National Hospital Organization, Kobe Medical Center, Kobe, Japan.; Department of Orthopaedic Surgery, Meijo Hospital, Nagoya, Japan.; Department of Orthopaedic Surgery, National Hospital Organization, Hokkaido Medical Center, Sapporo, Japan.; Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.; Department of Orthopaedic Surgery, Niigata University Medical and Dental General Hospital, Niigata, Japan.; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.; Department of Orthopaedic and Spine Surgery, Fukuoka Children's Hospital, Fukuoka, Japan.; Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan.; Department of Orthopaedic Surgery, Kyushu University Beppu Hospital, Beppu, Japan.; Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.; Department of Orthopaedic Surgery, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan.; Department of Orthopaedic Surgery, Teine Keijinkai Hospital, Sapporo, Japan.; Department of Orthopaedic Surgery Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.; Department of Orthopaedic Surgery, Jichi Medical University, Shimotsuke, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Department of Orthopaedic Surgery, Fujita Health University, Toyoake, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Department of Orthopaedic Surgery, International University of Health and Welfare School of Medicine, Narita, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.; Department of Orthopaedic Surgery, Kono Orthopaedic Clinic, Tokyo, Japan.; Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.; Department of Advanced Medicine for Spine and Spinal Cord Disorders, Hokkaido University Graduate School of Medicine, Sapporo, Japan.; Department of Preventive and Therapeutic Research for Metastatic Bone Tumor, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.; Center for Translational Research, Scottish Rite for Children, Dallas, TX, United States.; Department of Orthopaedic Surgery and Pediatric, University of Texas Southwestern Medical Center, Dallas, TX, United States.; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States.; Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental and University, Tokyo, Japan.; Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.; Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.; Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

DOI: 10.3389/fendo.2023.1089414

Patient Centred Factor

Triggers: Low body mass index

Clinical Imbalances

Structural Integrity and Musculoskeletal

Nutrition Evidence Keywords

BMI Body mass index Idiopathic scoliosis Genome-wide association studies (GWASs) Low body mass index Adolescent Adolescent idiopathic scoliosis Spinal deformity Genetic factors Japanese Caucasians

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Medical:

https://medlineplus.gov/scoliosis.html

MeSH Terms: Adolescent, Humans, Body Mass Index, Genome-Wide Association Study, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Scoliosis