Abstract: Objective To investigate the causal relationship between gut microbiota and short stature by genomewide Mendelian randomization(MR), in order to proride reference of clinical treatment of short statue. Methods Genus level gut microbiota genome-wide association study data of 18 340 samples was obtained from the MiBioGen as the exposure group, and genome-wide association study data of short stature were obtained from FinnGen R9 as the outcome group. The inverse variance weighting method was used as the main analysis method forMR analysis, and sensitivity analysis such as leave-one-out, heterogeneity test, and pleiotropy analysis were performed, reverse MR to rule out reverse causality. Results Prevotella9 (OR=1.76, 95%CI:1.10 - 2.82, P=0.018), Alloprevotella (OR=1.82, 95%CI:1.22 - 2.72, P=0.003), and FamilyXIIIAD3011group (OR=1.86, 95%CI:1.04 - 3.31, P=0.036) were positively correlated with the onset of short stature. Parasutterella (OR=0.58, 95%CI: 0.37 - 0.92, P=0.020), Clostridiumsensustricto1 (OR=0.50, 95%CI: 0.25 - 0.99, P=0.045), and Roseburia (OR=0.48, 95%CI:0.26 - 0.89, P=0.020) were negatively correlated with the onset of short stature. Conclusion Prevotella9, Alloprevotella, and FamilyXIIIAD3011group increase the risk of short stature, while Parasutterella, Clostridiumsensustricto1 and Roseburia have protective effects on the occurrence of short stature.

Key words: short stature, gut microbiota, mendelian randomization, genome-wide association study

摘要： 目的 利用孟德尔随机化(MR)方法探究肠道菌群与矮小症之间的因果关系,为矮小症的临床诊疗提供参考。方法 从MiBioGen联盟获得18 340个样本的属水平肠道菌群全基因组关联研究数据作为暴露组,从FinnGen联盟R9获取矮小症的全基因组关联研究数据作为结局组。采用逆方差加权法作为主要分析方法进行MR分析,并采用留一法、异质性检验、多效性检验等进行敏感性分析,反向MR以排除反向因果关系。结果 肠道菌群中Prevotella9 (OR=1.76, 95%CI:1.10~2.82,P=0.018)、Alloprevotella (OR=1.82, 95%CI:1.22~2.72,P=0.003)、FamilyXIIIAD3011group (OR=1.86, 95%CI:1.04~3.31,P=0.036)与矮小症的发病呈正相关; Parasutterella (OR=0.58, 95%CI:0.37~0.92, P=0.020)、Clostridiumsensustricto1 (OR=0.50, 95%CI:0.25~0.99, P=0.045)、Roseburia(OR=0.48, 95%CI:0.26~0.89, P=0.020)与矮小症的发病呈负相关。结论 肠道菌群中Prevotella9、Alloprevotella、FamilyXIIIAD3011group会增加矮小症的发生风险,Parasutterella、Clostridiumsensustricto1、Roseburia对矮小症的发生有保护作用。

关键词: 矮小症, 肠道菌群, 孟德尔随机化, 全基因组关联研究