Volume 24 Issue 6
Jun.  2026
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Article Navigation >  Chinese Journal of General Practice  > 2026  >  24(6): 962-967
LIU Liangshan, SHENG Jiagang, XU Ling, JI Siqin, SU Qiuling, LU Yajun, WANG Zhenwei. Bidirectional two-sample Mendelian randomization study on Alzheimer's disease and COPD[J]. Chinese Journal of General Practice, 2026, 24(6): 962-967. doi: 10.16766/j.cnki.issn.1674-4152.004531
Citation: LIU Liangshan, SHENG Jiagang, XU Ling, JI Siqin, SU Qiuling, LU Yajun, WANG Zhenwei. Bidirectional two-sample Mendelian randomization study on Alzheimer's disease and COPD[J]. Chinese Journal of General Practice, 2026, 24(6): 962-967. doi: 10.16766/j.cnki.issn.1674-4152.004531
shu

Bidirectional two-sample Mendelian randomization study on Alzheimer's disease and COPD

doi: 10.16766/j.cnki.issn.1674-4152.004531
  • 1.

    Department of Respiratory Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200080, China

Funds:

 81874515

 23S21900700

 2024QN013

 24KFL078

 17401970900

 RY411.37.03

  • Received Date: 2025-07-02
    Available Online: 2026-11-10
    Abstract
  •   Objective  Using bidirectional two-sample Mendelian randomization (MR), this study examines the causal associations between Alzheimer's disease (AD) and chronic obstructive pulmonary disease (COPD), as well as their pathological features and comorbidities, thereby providing evidence to inform clinical comorbidity management.  Methods  Data for Alzheimer's disease were obtained from the R9 (9 301 cases and 367 976 controls), R10 (10 520 cases and 401 661 controls), R11 (11 755 cases and 441 978 controls), and R12 (13 964 cases and 486 384 controls) releases of the Finnish database. Data for COPD, its pathological features, and comorbidities were sourced from the UK Biobank (UKB) database. The inverse-variance weighted (IVW) method was used to derive the primary causal estimates. To ensure the validity and robustness of the causal inferences, supplementary analyses were performed using MR-Egger, weighted median, simple mode, weighted mode, leave-one-out sensitivity analysis, MR-Egger intercept test, funnel plots, and forest plots.  Results  Forward MR analysis indicated that AD was significantly positively associated with the risk of COPD in the R9 (P=0.010), R10 (P=0.001), and R11 (P=0.011) datasets. A positive association between AD and the risk of emphysema was also observed in R11. Reverse MR analysis revealed that COPD was significantly negatively associated with AD in the R9 (P=0.048), R11 (P=0.046), and R12 (P=0.032) datasets. No evidence of a genetic causal relationship was identified between AD and the pathological features or comorbidities of COPD.  Conclusion  AD is a potential risk factor for COPD and emphysema, potentially mediated by AD-related neuroinflammation, neutrophil activation, and chronic hypoxia. Conversely, COPD may indirectly reduce the risk of AD by modulating oxidative stress and gut microbiota.

     

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