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

被引：4

作者：

Otomo, Nao ^{[1
,2
,3
]}

Khanshour, Anas M. ^{[4
]}

Koido, Masaru ^{[1
,5
]}

Takeda, Kazuki ^{[2
]}

Momozawa, Yukihide ^{[6
]}

Kubo, Michiaki ^{[6
]}

Kamatani, Yoichiro ^{[5
,7
]}

Herring, John A. ^{[8
,9
]}

Ogura, Yoji ^{[2
]}

Takahashi, Yohei ^{[2
]}

Minami, Shohei ^{[10
]}

Uno, Koki ^{[11
]}

Kawakami, Noriaki ^{[12
]}

Ito, Manabu ^{[13
]}

Sato, Tatsuya ^{[14
]}

Watanabe, Kei ^{[15
]}

Kaito, Takashi ^{[16
]}

Yanagida, Haruhisa ^{[17
]}

Taneichi, Hiroshi ^{[18
]}

Harimaya, Katsumi ^{[19
]}

Taniguchi, Yuki ^{[20
]}

Shigematsu, Hideki ^{[21
]}

Iida, Takahiro ^{[22
,23
]}

Demura, Satoru ^{[24
]}

Sugawara, Ryo ^{[25
]}

Fujita, Nobuyuki ^{[2
,26
]}

Yagi, Mitsuru ^{[2
,27
]}

Okada, Eijiro ^{[2
]}

Hosogane, Naobumi ^{[2
,28
]}

Kono, Katsuki ^{[2
,29
]}

Nakamura, Masaya ^{[2
]}

Chiba, Kazuhiro ^{[2
,26
]}

Kotani, Toshiaki ^{[10
]}

Sakuma, Tsuyoshi ^{[10
]}

Akazawa, Tsutomu ^{[10
]}

Suzuki, Teppei ^{[11
]}

Nishida, Kotaro ^{[30
]}

Kakutani, Kenichiro ^{[30
]}

Tsuji, Taichi ^{[12
]}

Sudo, Hideki ^{[31
]}

Iwata, Akira ^{[32
]}

Inami, Satoshi ^{[18
]}

Wise, Carol A. ^{[4
,9
,33
]}

Kochi, Yuta ^{[34
]}

Matsumoto, Morio ^{[2
]}

Ikegawa, Shiro ^{[3
]}

Watanabe, Kota ^{[2
]}

Terao, Chikashi ^{[1
,35
,36
]}

机构：

[1] RIKEN, RIKEN Ctr Integrat Med Sci, Lab Stat & Translat Genet, Yokohama, Japan

[2] Keio Univ, Dept Orthopaed Surg, Sch Med, Tokyo, Japan

[3] RIKEN Ctr Integrat Med Sci, Lab Bone & Joint Dis, Tokyo, Japan

[4] Scottish Rite Children, Ctr Translat Res, Dallas, TX USA

[5] Univ Tokyo, Inst Med Sci, Div Mol Pathol, Tokyo, Japan

[6] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Japan

[7] Univ Tokyo, Grad Sch Frontier Sci, Lab Complex Trait Genom, Tokyo, Japan

[8] Scottish Rite Children, Dept Orthopaed Surg, Dallas, TX USA

[9] Univ Texas Southwestern Med Ctr, Dept Orthopaed Surg & Pediat, Dallas, TX USA

[10] Seirei Sakura Citizen Hosp, Dept Orthopaed Surg, Sakura, Japan

[11] Kobe Med Ctr, Natl Hosp Org, Dept Orthopaed Surg, Kobe, Japan

[12] Meijo Hosp, Dept Orthopaed Surg, Nagoya, Japan

[13] Natl Hosp Org, Hokkaido Med Ctr, Dept Orthopaed Surg, Sapporo, Japan

[14] Juntendo Univ, Dept Orthopaed Surg, Sch Med, Tokyo, Japan

[15] Niigata Univ, Med & Dent Gen Hosp, Dept Orthopaed Surg, Niigata, Japan

[16] Osaka Univ, Dept Orthopaed Surg, Grad Sch Med, Suita, Japan

[17] Fukuoka Childrens Hosp, Dept Orthopaed & Spine Surg, Fukuoka, Japan

[18] Dokkyo Med Univ, Dept Orthopaed Surg, Sch Med, Mibu, Japan

[19] Kyushu Univ, Beppu Hosp, Dept Orthopaed Surg, Beppu, Japan

[20] Univ Tokyo, Fac Med, Dept Orthopaed Surg, Tokyo, Japan

[21] Nara Med Univ, Dept Orthopaed Surg, Kashihara, Japan

[22] Dokkyo Med Univ, Saitama Med Ctr, Dept Orthopaed Surg, Koshigaya, Japan

[23] Teine Keijinkai Hosp, Dept Orthopaed Surg, Sapporo, Japan

[24] Kanazawa Univ, Grad Sch Med Sci, Dept Orthopaed Surg, Kanazawa, Japan

[25] Jichi Med Univ, Dept Orthopaed Surg, Shimotsuke, Japan

[26] Fujita Hlth Univ, Dept Orthopaed Surg, Toyoake, Japan

[27] Int Univ Hlth & Welf, Sch Med, Dept Orthopaed Surg, Narita, Japan

[28] Natl Def Med Coll, Dept Orthopaed Surg, Tokorozawa, Japan

[29] Kono Orthopaed Clin, Dept Orthopaed Surg, Tokyo, Japan

[30] Kobe Univ, Dept Orthopaed Surg, Grad Sch Med, Kobe, Japan

[31] Hokkaido Univ, Dept Adv Med Spine & Spinal Cord Disorders, Grad Sch Med, Sapporo, Japan

[32] Hokkaido Univ, Fac Med, Grad Sch Med, Dept Prevent & Therapeut Res Metastat Bone Tumor, Sapporo, Japan

[33] Univ Texas Southwestern Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX USA

[34] Tokyo Med & Dent & Univ, Med Res Inst, Dept Genom Funct & Divers, Tokyo, Japan

[35] Shizuoka Prefectural Gen Hosp, Clin Res Ctr, Shizuoka, Japan

[36] Univ Shizuoka, Sch Pharmaceut Sci, Dept Appl Genet, Shizuoka, Japan

来源：

FRONTIERS IN ENDOCRINOLOGY | 2023年 / 14卷

关键词：

adolescent idiopathic scoliosis; body mass index; Mendelian randomization (MR); genetic study; genome-wide association study; GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; INSTRUMENTS; METAANALYSIS; PREVALENCE; FEMALE; TWINS; LOCI;

D O I：

10.3389/fendo.2023.1089414

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 10(-3)), weighted median method (beta = -0.56 [0.18], p = 8.5 x 10(-3)) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 x 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.

引用

页数：11

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