Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate
Background The causal association between particulate matter 2.5 (PM2.5) and Alzheimer’s disease (AD) remains inconclusive, and the mediators of the association have yet to be explored.Aims We aimed to assess the potential causal relationship between PM2.5 and AD, and to investigate the mediating ro...
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Taylor & Francis Group
2024-12-01
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| Series: | Annals of Human Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/03014460.2024.2337731 |
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| author | Zehan Huang Guodong He Shuo Sun Yuqing Huang |
| author_facet | Zehan Huang Guodong He Shuo Sun Yuqing Huang |
| author_sort | Zehan Huang |
| collection | DOAJ |
| description | Background The causal association between particulate matter 2.5 (PM2.5) and Alzheimer’s disease (AD) remains inconclusive, and the mediators of the association have yet to be explored.Aims We aimed to assess the potential causal relationship between PM2.5 and AD, and to investigate the mediating role of dehydroepiandrosterone sulphate (DHEAS).Subjects and methods We implemented a two-sample Mendelian randomisation (MR) study to examine the genetic predisposition to PM2.5 exposure and its association with AD. The inverse-variance weighted (IVW) method served as the primary analytical tool to estimate the odds ratio (OR) and 95% confidence interval (95% CI).Results There were 6 and 4 genetic variants associated with DHEAS and PM2.5, respectively. Based on the multivariable MR analysis, we found that after adjusting for DHEAS, each standard deviation increase in PM2.5 was associated with the risk of AD (OR: 2.96, 95% CI: 1.33, 6.58, p = 0.00769). The MR Egger intercept test did not detect horizontal pleiotropy for PM2.5 (P-pleiotropy = 0.879) and DHEAS(P-pleiotropy = 0.941). According to the results of the mediation analysis, DHEAS accounted for 18.3% of the association between PM2.5 and AD.Conclusion Our findings affirm a significant causal association between PM2.5 exposure and AD, with DHEAS playing a mediating role in this relationship. |
| format | Article |
| id | doaj-art-e323a65f71b24b1bba1548529bf8b1ca |
| institution | DOAJ |
| issn | 0301-4460 1464-5033 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Annals of Human Biology |
| spelling | doaj-art-e323a65f71b24b1bba1548529bf8b1ca2025-08-20T02:40:35ZengTaylor & Francis GroupAnnals of Human Biology0301-44601464-50332024-12-0151110.1080/03014460.2024.2337731Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphateZehan Huang0Guodong He1Shuo Sun2Yuqing Huang3Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, ChinaResearch Department of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, ChinaBackground The causal association between particulate matter 2.5 (PM2.5) and Alzheimer’s disease (AD) remains inconclusive, and the mediators of the association have yet to be explored.Aims We aimed to assess the potential causal relationship between PM2.5 and AD, and to investigate the mediating role of dehydroepiandrosterone sulphate (DHEAS).Subjects and methods We implemented a two-sample Mendelian randomisation (MR) study to examine the genetic predisposition to PM2.5 exposure and its association with AD. The inverse-variance weighted (IVW) method served as the primary analytical tool to estimate the odds ratio (OR) and 95% confidence interval (95% CI).Results There were 6 and 4 genetic variants associated with DHEAS and PM2.5, respectively. Based on the multivariable MR analysis, we found that after adjusting for DHEAS, each standard deviation increase in PM2.5 was associated with the risk of AD (OR: 2.96, 95% CI: 1.33, 6.58, p = 0.00769). The MR Egger intercept test did not detect horizontal pleiotropy for PM2.5 (P-pleiotropy = 0.879) and DHEAS(P-pleiotropy = 0.941). According to the results of the mediation analysis, DHEAS accounted for 18.3% of the association between PM2.5 and AD.Conclusion Our findings affirm a significant causal association between PM2.5 exposure and AD, with DHEAS playing a mediating role in this relationship.https://www.tandfonline.com/doi/10.1080/03014460.2024.2337731ambient particulate matter 2.5Alzheimer’s diseasedehydroepiandrosterone sulphateMendelian randomisationmediation analysis |
| spellingShingle | Zehan Huang Guodong He Shuo Sun Yuqing Huang Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate Annals of Human Biology ambient particulate matter 2.5 Alzheimer’s disease dehydroepiandrosterone sulphate Mendelian randomisation mediation analysis |
| title | Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate |
| title_full | Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate |
| title_fullStr | Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate |
| title_full_unstemmed | Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate |
| title_short | Causal relationship of genetically predicted particulate matter 2.5 level with Alzheimer’s disease and the mediating effect of dehydroepiandrosterone sulphate |
| title_sort | causal relationship of genetically predicted particulate matter 2 5 level with alzheimer s disease and the mediating effect of dehydroepiandrosterone sulphate |
| topic | ambient particulate matter 2.5 Alzheimer’s disease dehydroepiandrosterone sulphate Mendelian randomisation mediation analysis |
| url | https://www.tandfonline.com/doi/10.1080/03014460.2024.2337731 |
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