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 randomization (MR) analysis. The 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 FEV1/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 chronic obstructive pulmonary disease (COPD), asthma, and FEV1/FVC < 70%, and to perform non-linear 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 (0.024, 0.086)]. The PGS for increased eGFR showed a significant association with a reduced risk of FEV1/FVC < 70% [OR 0.93 (0.87, 0.99)], COPD [OR 0.93 (0.87, 0.99)] and late-onset (≥ 50 years old) asthma [OR 0.93 (0.88, 0.99)]. The non-linear MR demonstrated that the causal effect from eGFR to FEV1/FVC was apparent in eGFR ranges lower than 60 mL/min/1.73 m2. On the other hand, genetically predicted FEV1/FVC showed non-significant causal estimates of eGFR change [beta 0.568% (-0.458, 1.605%)]. Conclusion: This study supports kidney function impairment would be a causative factor for obstructive lung disease.