Causal effects of lung function and COPD on functional outcome following IS: a univariable and multivariable MR study

Background and ObjectivesStudies have shown that lung function and chronic obstructive pulmonary disease (COPD) are associated with functional outcome for several diseases, as well as the onset of stroke. However, the causal relationship between lung function, COPD and the functional outcome of ischemic stroke (IS) is unclear. The aim of this study was to investigate the causal relationship between lung function, COPD and IS functional outcomes using Mendelian randomization (MR). MethodsLung function data were derived from the Genome-wide Association Study (GWAS) summary database. Data of COPD were derived from the national genetic factors data repository of the FinnGen project in Finland. The outcome data of IS function were obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) Network. Univariate MR analysis mainly used the inverse variance weighting (IVW) method, MR-Egger, weighted median method and two-sample Maximum Likelihood to evaluate the causal effects of lung function and COPD on the prognosis of IS. Sensitivity analyses were conducted by evaluating heterogeneity and potential pleiotropy. Additionally, multivariable MR analyses were employed to ascertain whether these effects were independent. ResultsIn univariate MR analyses, the estimates of IVW, MR-Egger, weighted median method and two-sample Maximum Likelihood analysis all showed that there was no genetic causal relationship between COPD, FVC, FEV1, FEV1/FVC, PEF and functional outcome after IS (P>0.05). Sensitivity analyses yielded no evidence of directional pleiotropy or substantial heterogeneity. Multivariable MR analyses demonstrated that, after adjustment for insomnia, smoking initiation, waist-to-hip ratio(WHR) or depression, both COPD and PEF exhibited a causal association with adverse functional outcome following IS. ConclusionOur research indicated that at the level of genetic causality, no significant associations were observed between lung function indices (FEV1, FVC, FEV1/FVC, PEF) or COPD and functional outcome following IS. Our discovery may challenge the conventional notion that "improving lung function itself can efficiently promote the prognosis of IS function". Future research needs to further explore other possible causal pathways and consider various factors comprehensively to develop more effective rehabilitation strategies after IS.