Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 1: 87 - 94

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.01.010

Public health

Two-sample Mendelian randomization study on the causal association between air pollution and Alzheimer′s disease

  • ZHANG Yingying ,
  • ZHANG Junyao ,
  • SONG Jiwei ,
  • WANG Shengjie ,
  • YAO Junyan
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  • 1.Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
    2.Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
YAO Junyan, E-mail: sunshineyao@163.com.

Received date: 2024-06-10

  Accepted date: 2024-10-02

  Online published: 2025-01-17

Supported by

National Natural Science Foundation of China(82171183);Medical Talent Training Program of Shanghai Pudong New Area Health Commission(PWR12023-01)

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Abstract

Objective ·To explore the causal relationship between air pollution and the risk of Alzheimer′s disease (AD) by using two-sample Mendelian randomization (MR). Methods ·Based on the data from the genome-wide association study (GWAS), a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD. Air pollution indicators, including particulate matter 2.5 (PM2.5), particulate matter 2.5-10 (PM2.5-10), particulate matter 10 (PM10), nitrogen dioxide and nitrogen oxides, were used as exposure factors, and summarized data were aggregated from the UK Biobank database. The PM2.5 dataset included 423 796 cases, with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms (SNPs); the PM2.5-10 dataset included 423 796 cases, with correlation analysis conducted on 9 851 867 SNPs; the PM10 dataset included 455 314 cases, with correlation analysis conducted on 9 851 867 SNPs; the nitrogen dioxide dataset included 456 380 cases, with correlation analysis conducted on 9 851 867 SNPs; the nitrogen oxides dataset included 456 380 cases, with correlation analysis conducted on 9 851 867 SNPs. AD was used as the outcome factor, and data were obtained from the International Genomics of Alzheimer′s Project (IGAP). The AD dataset included 25 580 cases and 48 466 controls, with correlation analysis of 7 067 513 SNPs. SNPs significantly associated with AD were used as instrumental variables. The main analysis was conducted by using the inverse variance weighted (IVW) method, and four methods including weighted median, MR-Egger regression, mode-based simple estimation and mode-based weighted estimation were used for quality control. Heterogeneity testing, gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results. Results ·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD (both IVW and MR-Egger results, P>0.05). Gene pleiotropy testing did not detect any pleiotropic effects (MR-Egger results, P>0.05). Sensitivity analysis confirmed the stability of the PM2.5 results. IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations (P<0.001), while no statistically significant associations were observed between PM2.5-10 (P=0.664), PM10 (P=0.664), nitrogen dioxide (P=0.284), nitrogen oxides (P=0.567) and AD. Conclusion ·There is a significant causal relationship between PM2.5 exposure and the risk of AD, with PM2.5 exposure increasing the incidence of AD. However, no evidence has been found to suggest that PM2.5-10, PM10, nitrogen dioxide or nitrogen oxides cause an increased risk of AD.

Key words： Alzheimer′s disease (AD); air pollution; Mendelian randomization (MR); causal inference

Cite this article

ZHANG Yingying , ZHANG Junyao , SONG Jiwei , WANG Shengjie , YAO Junyan . Two-sample Mendelian randomization study on the causal association between air pollution and Alzheimer′s disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(1) : 87 -94 . DOI: 10.3969/j.issn.1674-8115.2025.01.010

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