肥胖与慢性阻塞性肺疾病因果关系的孟德尔随机化研究

A Mendelian randomization study on the causal relationship between obesity and chronic obstructive pulmonary disease

目的本研究通过使用孟德尔随机化分析方法探究肥胖与慢性阻塞性肺疾病(慢阻肺)之间的因果关系。方法采用全基因组关联分析数据筛选体重指数(BMI)、腰围、腹部皮下脂肪体积和内脏脂肪体积的肥胖相关单核苷酸多态性作为工具变量。以逆方差加权法作为孟德尔随机化分析的主要方法。用加权中值法、MR-Egger回归法、简易模式法和加权模式法检测主分析的稳健性。通过比较OR值和95%CI探讨肥胖与慢阻肺之间的关联性。结果BMI(OR=1.149,95%CI:1.114~1.184,P<0.01)、腰围(OR=1.151,95%CI:1.108~1.195,P<0.01)、内脏脂肪体积(OR=1.080,95%CI:0.998~1.168,P=0.013)不仅与肺功能受损有关,与慢阻肺风险增加也有关(BMI:OR=1.529,95%CI:1.349~1.733,P<0.01;腰围:OR=1.799,95%CI:1.522~2.128,P<0.01;内脏脂肪体积:OR=1.421,95%CI:1.019~1.981,P=0.038)。而腹部皮下脂肪体积与肺功能(OR=1.080,95%CI:1.016~1.147,P=0.056)和慢阻肺(OR=1.151,95%CI:0.878~1.508,P=0.310)均没有因果关系。结论肥胖特别是内脏脂肪过度积聚影响肺功能,增加慢阻肺风险,而腹部皮下脂肪与慢阻肺无关。

ObjectiveTo explore the causal relationship between obesity and chronic obstructive pulmonary disease(COPD)by using Mendelian randomization analysis.MethodsThe single nucleotide polymorphisms(SNPs)that arerelated to obesity measures,such as body mass index(BMI),waist circumference,visceral adipose tissue volume,and abdominal subcutaneous adipose tissue volume,from published available genome-wide association study(GWAS)were selected as instrumental variables.The inverse-variance weighted method was used as the main method forMendelian randomization analysis.Four complementary methods(weighted median method,MR-Egger method,simple mode,and weighted mode)were used for robustness checks.Through comparison of odds ratio(OR)values and 95%confidence intervals(CI),the study investigated the relationship between obesityand COPD.ResultsLung function is related to BMI(OR=1.149,95%CI:1.114-1.184,P<0.01),waist circumference(OR=1.151,95%CI:1.108-1.195,P<0.01),and visceral fat volume(OR=1.080,95%CI:0.998-1.168,P=0.013),but not to subcutaneous abdominal fat(OR=1.080,95%CI:1.016-1.147,P=0.056).Similar relationships were also observed in COPD(BMI:OR=1.529,95%CI:1.349-1.733,P<0.01;waist circumference:OR=1.799,95%CI:1.522-2.128,P<0.01;visceral fatvolume:OR=1.421,95%CI:1.019-1.981,P=0.038),but not tosubcutaneous abdominal fat(OR=1.151,95%CI:0.878-1.508,P=0.310).ConclusionsObesity characterized by increased visceral fat associates with a decline in lung function and a high risk of COPD,while there is noassociationbetween increased subcutaneous fat and COPD.