Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.
Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.
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DOI：
10.3389/fendo.2023.1089414
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发表时间：
2023
影响因子：
5.2
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中科院分区：
文献类型：
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青少年特发性脊柱侧凸(AIS)是一种脊柱三维畸形的疾病，是影响1-5%青少年的常见病。AIS也被认为是一种涉及环境和遗传因素的复杂疾病。从流行病学和遗传学角度来看，AIS与体重指数(BMI)之间存在一定的关系。然而，AIS和BMI之间的因果关系仍有待阐明。孟德尔随机化(MR)分析使用来自AIS(日本队列，5,327例，73,884个对照；美国队列：1,468例，20,158个对照)和BMI(生物库日本：173430个个体；人体测量特征遗传调查的荟萃分析：806334个个体；欧洲儿童队列：39620个个体；使用基因组学和流行病学的种群结构：49335个个体)的全基因组关联研究(GWAS)的汇总统计数据。在评估BMI对AIS的影响的MR分析中，使用日本的逆方差加权(IVW)方法、加权中位数方法和Egger回归(MR-Egger)方法来评估BMI和AIS汇总统计之间的关联。BMI遗传性降低对AIS风险的显著因果关系估计分别为：IVW法(估计(Beta)[SE]=-0.56[0.16]，p=1.8×10-3)、加权中位数法(beta=-0.56[0.18]，p=8.5×10-3)和MR-Egger法(beta=-1.50[0.43]，p=4.7×10-3)。在三种MR方法中使用美国AIS汇总统计数据时，也观察到了一致的结果；然而，当评估AIS对BMI的影响时，没有观察到显著的因果关系。我们的孟德尔随机化分析使用了对AIS和GWAS的大型研究，对BMI汇总统计表明，导致低BMI的遗传变异对AIS的发病有因果影响。这一结果与流行病学研究结果一致，有助于AIS的早期发现。
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. 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. 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. 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.