Abstract:
Observational studies have suggested an association between air pollutants and congenital malformations; however, conclusions are inconsistent and the causal associations have not been elucidated. In this study, based on publicly available genetic data, a two-sample Mendelian randomization (MR) was applied to explore the associations between particulate matter 2.5 (PM2.5), NOX, NO2 levels and 11 congenital malformations. Inverse variance weighted (IVW), MR-Egger and weighted median were used as analytical methods, with IVW being the main method. A series of sensitivity analyses were used to verify the robustness of the results. For significant associations, multivariable MR (MVMR) was utilized to explore possible mediating effects. The IVW results showed that PM2.5 was associated with congenital malformations of digestive system (OR = 7.72, 95 %CI = 2.33-25.54, P = 8.11E-4) and multiple systems (OR = 8.63, 95 %CI = 1.02-73.43, P = 0.048) risks; NOX was associated with circulatory system (OR = 4.65, 95 %CI = 1.15-18.86, P = 0.031) and cardiac septal defects (OR = 14.09, 95 %CI = 1.62-122.59, P = 0.017) risks; NO2 was correlated with digestive system (OR = 27.12, 95 %CI = 1.81-407.07, P = 0.017) and cardiac septal defects (OR = 22.57, 95 %CI = 2.50-203.45, P = 0.005) risks. Further MVMR analyses suggest that there may be interactions in the effects of these air pollutants on congenital malformations. In conclusion, this study demonstrated a causal association between air pollution and congenital malformations from a genetic perspective.
摘要:
观察性研究表明,空气污染物与先天性畸形之间存在关联;然而,结论不一致,因果关系尚未阐明.在这项研究中,基于公开的遗传数据,双样本孟德尔随机化(MR)应用于探索颗粒物2.5(PM2.5)之间的关联,NOX,NO2水平和11种先天性畸形。反向方差加权(IVW),MR-Egger和加权中位数作为分析方法,IVW是主要方法。使用一系列灵敏度分析来验证结果的稳健性。对于重要的协会,利用多变量MR(MVMR)来探索可能的中介效应。IVW结果显示,PM2.5与消化系统先天性畸形(OR=7.72,95CI=2.23-25.24,P=8.11E-4)和多系统(OR=8.63,95CI=1.02-73.43,P=0.048)风险相关;NOX与循环系统(OR=4.65,95CI=1.15-18.86,P=0.081,室间隔1.95-P=2.59)风险相关(OR=1.25进一步的MVMR分析表明,这些空气污染物对先天性畸形的影响可能存在相互作用。总之,这项研究从遗传角度证明了空气污染与先天畸形之间的因果关系。