TY - JOUR T1 - Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00848-2021 VL - 58 IS - 6 SP - 2100848 AU - Sehoon Park AU - Soojin Lee AU - Yaerim Kim AU - Semin Cho AU - Kwangsoo Kim AU - Yong Chul Kim AU - Seung Seok Han AU - Hajeong Lee AU - Jung Pyo Lee AU - Kwon Wook Joo AU - Chun Soo Lim AU - Yon Su Kim AU - Dong Ki Kim Y1 - 2021/12/01 UR - http://erj.ersjournals.com/content/58/6/2100848.abstract N2 - 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; β=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 (β=0.568%, 95% CI −0.458–1.605%).Conclusion This study supports kidney function impairment as a causative factor for obstructive lung disease.This Mendelian randomisation study identified that genetically predicted eGFR loss was associated with decrease in FEV1/FVC and increase in the risk of COPD and late-onset asthma. The causal estimates from FEV1/FVC to eGFR were nonsignificant. https://bit.ly/3eC99uT ER -