Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study
Rationale Large retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors....
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BMJ Publishing Group
2021-01-01
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| Series: | BMJ Open Respiratory Research |
| Online Access: | https://bmjopenrespres.bmj.com/content/8/1/e000759.full |
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| author | George Davey Smith Raquel Granell James Dodd Daniel Higbee Esther Walton Roxanna Korologou-Linden |
| author_facet | George Davey Smith Raquel Granell James Dodd Daniel Higbee Esther Walton Roxanna Korologou-Linden |
| author_sort | George Davey Smith |
| collection | DOAJ |
| description | Rationale Large retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.Objectives To examine a causal relationship between COPD, lung function and Alzheimer’s disease.Methods Using two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.Results We found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).Conclusion Neither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly. |
| format | Article |
| id | doaj-art-8bc5f47504d649179cbe00577b06e27d |
| institution | OA Journals |
| issn | 2052-4439 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Respiratory Research |
| spelling | doaj-art-8bc5f47504d649179cbe00577b06e27d2025-08-20T02:22:17ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392021-01-018110.1136/bmjresp-2020-000759Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation studyGeorge Davey Smith0Raquel Granell1James Dodd2Daniel Higbee3Esther Walton4Roxanna Korologou-Linden54 Department of Social Medicine, MRC Centre for Causal Analyses in Translational Epidemiology, Bristol, UKDepartment of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UKAcademic Respiratory Unit, Southmead Hospital, Bristol, UK1 Department of Psychology, University of Bath, Bath, UKMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UKRationale Large retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.Objectives To examine a causal relationship between COPD, lung function and Alzheimer’s disease.Methods Using two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.Results We found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).Conclusion Neither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.https://bmjopenrespres.bmj.com/content/8/1/e000759.full |
| spellingShingle | George Davey Smith Raquel Granell James Dodd Daniel Higbee Esther Walton Roxanna Korologou-Linden Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study BMJ Open Respiratory Research |
| title | Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study |
| title_full | Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study |
| title_fullStr | Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study |
| title_full_unstemmed | Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study |
| title_short | Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study |
| title_sort | examining the possible causal relationship between lung function copd and alzheimer s disease a mendelian randomisation study |
| url | https://bmjopenrespres.bmj.com/content/8/1/e000759.full |
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