Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study

Abstract

Background Additional study is warranted to investigate the causal effects between kidney function and obstructive lung disease. Methods This study was a bidirectional two-sample Mendelian randomisation (MR) analysis. The Chronic Kidney Disease Genetics (CKDGen) genome-wide association study (GWAS) meta-analysis for estimated glomerular filtration rate (eGFR) including individuals of European ancestry (n=567 460) provided the genetic instrument for kidney function and outcome summary statistics. A GWAS for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) including individuals of European ancestry from the UK Biobank (n=321 047) provided the genetic instrument for FEV1/FVC and outcome data. A polygenic score (PGS) analysis was performed to test the causal estimates from kidney function to binary obstructive lung disease outcomes, including COPD, asthma and FEV1/FVC <70%, and to perform nonlinear MR with individual-level UK Biobank data. Results The causal estimates by summary-level MR indicated that genetically predicted increased kidney function was significantly associated with increased FEV1/FVC z-scores (10% increase in eGFR; beta=0.055, 95% CI 0.024-0.086). The PGS for increased eGFR showed a significant association with a reduced risk of FEV1/FVC <70% (OR 0.93, 95% CI 0.87-0.99), COPD (OR 0.93, 95% CI 0.87-0.99) and late-onset (age > 50 years) asthma (OR 0.93, 95% CI 0.88-0.99). The nonlinear MR demonstrated that the causal effect from eGFR to FEV1/FVC was apparent in eGFR ranges <60 mL.min(-1).1.73 m(-2). Conversely, genetically predicted FEV1/FVC showed nonsignificant causal estimates of eGFR change (beta=0.568%, 95% CI -0.458-1.605%). Conclusion This study supports kidney function impairment as a causative factor for obstructive lung disease.