Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study
Background: Increasing evidence has shown a link between immune cells and Alzheimer's disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between 731 immune cell signatures and AD in this study. Methods: We extracted gen...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556524000135 |
| _version_ | 1827341766742769664 |
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| author | Hua Xue Jiajia Chen Li Zeng Wenhui Fan |
| author_facet | Hua Xue Jiajia Chen Li Zeng Wenhui Fan |
| author_sort | Hua Xue |
| collection | DOAJ |
| description | Background: Increasing evidence has shown a link between immune cells and Alzheimer's disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between 731 immune cell signatures and AD in this study. Methods: We extracted genetic variants of 731 immune cell traits and AD from the publicly available GWAS dataset. The immune features included median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC) and morphological parameters (MP). The inverse variance weighted (IVW) method was the main MR analysis method, and sensitivity analyses were used to validate the robustness, heterogeneity and horizontal pleiotropy of the results. Results: After FDR adjustment, seven immune phenotypes were found to be associated significantly with AD risk: HLA DR on CD33− HLA DR+ (OR = 0.938, PFDR = 0.001), Secreting Treg %CD4 (OR = 0.972, PFDR = 0.021), HLA DR+ T cell AC (OR = 0.928, PFDR = 0.041), Activated & resting Treg % CD4 Treg (OR = 1.031, PFDR = 0.002), CD33 on CD33dim HLA DR+ CD11b+ (OR = 1.025, PFDR = 0.025), CD33 on CD14+ monocyte (OR = 1.026, PFDR = 0.027) and CD33 on CD66b++ myeloid cell (OR = 1.027, PFDR = 0.036). Conclusions: These findings demonstrated seven immune phenotypes were significantly associated with AD risk. This may provide researchers with a new perspective in exploring the biological mechanisms of AD and may lead to the exploration of earlier treatment. |
| first_indexed | 2024-03-07T21:54:42Z |
| format | Article |
| id | doaj.art-d5d67f76632b40e5bfa569d4dfc4ba1c |
| institution | Directory Open Access Journal |
| issn | 1873-6815 |
| language | English |
| last_indexed | 2024-03-07T21:54:42Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj.art-d5d67f76632b40e5bfa569d4dfc4ba1c2024-02-25T04:34:43ZengElsevierExperimental Gerontology1873-68152024-03-01187112371Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization studyHua Xue0Jiajia Chen1Li Zeng2Wenhui Fan3Department of Neurology, Sichuan Taikang Hospital, Chengdu, Sichuan, China; Corresponding authors at: Department of Neurology, Sichuan Taikang Hospital, No.881 Xianghe No.1 Street, Huayang Street, Tianfu New District, Sichuan 610213, China.College of Chemical Engineering, Sichuan University of Science & Engineering, Zigong, ChinaDepartment of Respiratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, ChinaDepartment of Neurology, Sichuan Taikang Hospital, Chengdu, Sichuan, China; Corresponding authors at: Department of Neurology, Sichuan Taikang Hospital, No.881 Xianghe No.1 Street, Huayang Street, Tianfu New District, Sichuan 610213, China.Background: Increasing evidence has shown a link between immune cells and Alzheimer's disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between 731 immune cell signatures and AD in this study. Methods: We extracted genetic variants of 731 immune cell traits and AD from the publicly available GWAS dataset. The immune features included median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC) and morphological parameters (MP). The inverse variance weighted (IVW) method was the main MR analysis method, and sensitivity analyses were used to validate the robustness, heterogeneity and horizontal pleiotropy of the results. Results: After FDR adjustment, seven immune phenotypes were found to be associated significantly with AD risk: HLA DR on CD33− HLA DR+ (OR = 0.938, PFDR = 0.001), Secreting Treg %CD4 (OR = 0.972, PFDR = 0.021), HLA DR+ T cell AC (OR = 0.928, PFDR = 0.041), Activated & resting Treg % CD4 Treg (OR = 1.031, PFDR = 0.002), CD33 on CD33dim HLA DR+ CD11b+ (OR = 1.025, PFDR = 0.025), CD33 on CD14+ monocyte (OR = 1.026, PFDR = 0.027) and CD33 on CD66b++ myeloid cell (OR = 1.027, PFDR = 0.036). Conclusions: These findings demonstrated seven immune phenotypes were significantly associated with AD risk. This may provide researchers with a new perspective in exploring the biological mechanisms of AD and may lead to the exploration of earlier treatment.http://www.sciencedirect.com/science/article/pii/S0531556524000135Alzheimer's diseaseImmune cellsCausal associationMendelian randomizationCD33 |
| spellingShingle | Hua Xue Jiajia Chen Li Zeng Wenhui Fan Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study Experimental Gerontology Alzheimer's disease Immune cells Causal association Mendelian randomization CD33 |
| title | Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study |
| title_full | Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study |
| title_fullStr | Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study |
| title_full_unstemmed | Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study |
| title_short | Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study |
| title_sort | causal relationship between circulating immune cells and the risk of alzheimer s disease a mendelian randomization study |
| topic | Alzheimer's disease Immune cells Causal association Mendelian randomization CD33 |
| url | http://www.sciencedirect.com/science/article/pii/S0531556524000135 |
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