肥胖和支气管哮喘之间的因果关联:一项双向孟德尔随机化研究

Causal association between obesity and bronchial asthma:A bidirectional Mendelian randomization study

目的探讨肥胖与支气管哮喘(哮喘)的因果关联,为哮喘的防治提供参考。方法本研究为双向孟德尔随机化研究。通过与体质量指数(BMI)、哮喘相关的2项全基因组关联研究,收集单核苷酸多态性(SNP)资料。采用逆方差加权法随机效应模型(IVW-RE)、孟德尔随机化Egger回归法(MR-Egger)、加权中位数法和加权众数法。以BMI相关的370个SNP作为工具变量,以哮喘作为研究结局进行正向孟德尔随机化(MR)分析。以哮喘相关的56个SNP作为工具变量,以BMI作为研究结局进行反向MR分析。结果IVW-RE结果显示,BMI与哮喘具有显著的因果关联,BMI每增加1个标准差,哮喘发病风险约增加1.26倍(OR=1.26,95%CI:1.19~1.33,P<0.001),在MR-Egger(OR=1.17,95%CI:1.01~1.36,P=0.035)、加权中位数法(OR=1.20,95%CI:1.11~1.29,P<0.001)和加权众数法(OR=1.15,95%CI:1.03~1.29,P=0.015)分析中同样发现BMI与哮喘具有正向因果关联。此外,使用IVW-RE进行反向MR分析,没有发现哮喘对BMI有影响的证据(OR=0.99,95%CI:0.98~1.00,P=0.193)。结论MR分析表明,成人BMI与哮喘的患病率存在因果关系,而哮喘对成人BMI的影响可能性很小。

Objective To investigate the causal relationship between obesity and bronchial asthma(asthma),so as to provide insights for the prevention and treatment of asthma.Methods This study was a bidirectional Mendelian randomization study.The data on single nucleotide polymorphism(SNP)were collected from two Genome-wide association studies(GWAS)on body mass index(BMI)and asthma.Four regression models including the inverse variance weighted random effects model(IVW-RE),MR-Egger regression,weighted median model,and weighted mode were performed for analysis.Forward Mendelian randomization(MR)was conducted using 370 BMI-related SNPs as instrumental variables and asthma as the study outcome.Reverse MR was performed with 56 asthma-related SNPs as instrumental variables and BMI as the study outcome.Results Results from IVW-RE demonstrated a significant causal association between BMI and asthma,with a 1 standard deviation increase in BMI resulting in a 1.26 times higher risk of asthma(OR=1.26,95%CI:1.19-1.33,P<0.001).This finding was consistent with results from MR-Egger regression(OR=1.17,95%CI:1.01-1.36,P=0.035),weighted median(OR=1.20,95%CI:1.11-1.29,P<0.001),and weighted mode(OR=1.15,95%CI:1.03-1.29,P=0.015).However,the IVW-RE results did not show any evidence of asthma affecting BMI(OR=0.99,95%CI:0.98-1.00,P=0.193).Conclusions MR analysis shows that there is a causal relationship between adult BMI and the prevalence of asthma.However,the effect of asthma on adult BMI is less probable.