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 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 nonsignificant 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Park has nothing to disclose.
Conflict of interest: Dr. Lee has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Cho has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Han has nothing to disclose.
Conflict of interest: Dr. Lee has nothing to disclose.
Conflict of interest: Dr. Lee has nothing to disclose.
Conflict of interest: Dr. Joo has nothing to disclose.
Conflict of interest: Dr. Lim has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
Conflict of interest: Dr. Kim has nothing to disclose.
- Received February 13, 2021.
- Accepted April 26, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org