| Title: | Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study |
| Journal: | European Respiratory Journal |
| Published: | 6 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33958431/ |
| DOI: | https://doi.org/10.1183/13993003.00848-2021 |
| URL: | https://erj.ersjournals.com/content/erj/58/6/2100848.full.pdf |
| Citations: | 18 (10 in last 2 years) as of 8 Aug 2024 |
Publication 5298
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Abstract
BACKGROUND: Additional study is warranted to investigate the causal effects between kidney function and obstructive lung disease.</p>
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.</p>
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%).</p>
CONCLUSION: This study supports kidney function impairment as a causative factor for obstructive lung disease.</p>
9 Keywords
- Asthma
- Forced Expiratory Volume
- Genome-Wide Association Study
- Humans
- Kidney
- Lung
- Middle Aged
- Pulmonary Disease, Chronic Obstructive
- Vital Capacity
13 Authors
- Sehoon Park
- Soojin Lee
- Yaerim Kim
- Semin Cho
- Kwangsoo Kim
- Yong Chul Kim
- Seung Seok Han
- Hajeong Lee
- Jung Pyo Lee
- Kwon Wook Joo
- Chun Soo Lim
- Yon Su Kim
- Dong Ki Kim
Enabling scientific discoveries that improve human health