Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization
ABSTRACT Background The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse i...
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Wiley
2025-01-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70263 |
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| author | Liumei Mo Wei Pan Wenjing Cao Kui Wang Li'an Huang |
| author_facet | Liumei Mo Wei Pan Wenjing Cao Kui Wang Li'an Huang |
| author_sort | Liumei Mo |
| collection | DOAJ |
| description | ABSTRACT Background The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse immune cells and ICH using Mendelian randomization (MR) analysis. Methods Genetic variants associated with 731 immune cell traits were sourced from a comprehensive genome‐wide association study (GWAS) involving 3757 participants. Summary statistics data for ICH were acquired from FinnGen, comprising 4056 ICH cases and 371,717 controls. The principal analytical tool utilized in our study was the inverse‐variance weighted (IVW) method, incorporated as a key component of a two‐sample MR approach. To mitigate potential biases and verify the stability of the conclusions drawn from the primary analytical methods, a series of sensitivity analyses were performed. Results MR analysis elucidated 33 immune cell traits with causal associations, comprising B cells (eight traits), conventional dendritic cells (cDC, two traits), maturation stages of T cells (two traits), monocytes (two traits), myeloid cells (five traits), TBNK cells (six traits), and regulatory T cells (Treg, eight traits). DP (CD4+CD8+) %T cell (OR = 0.83, CI = 0.72–0.96, p = 0.013) exhibited the strongest protective effect. In contrast, transitional AC (OR = 1.09, CI = 1.02–1.16, p = 0.006) and IgD− CD27− %lymphocyte (OR = 1.08, CI = 1.00–1.17, p = 0.045) showed a higher tendency to increase the ICH risk. The sensitivity analyses validated the robustness and consistency of these results. Conclusion Our research provides robust evidence substantiating the causal relationship between specific immunophenotypes and ICH risk. The identification of these findings significantly enhances our understanding of the pathogenic mechanisms underlying ICH, particularly pertaining to the immune system. This breakthrough paves the way for innovative clinical and pharmaceutical research opportunities, potentially promoting the development of targeted therapies and enhanced strategies for managing and preventing ICH. |
| format | Article |
| id | doaj-art-2e4524cf4357427785332fc9b9baf5a2 |
| institution | Kabale University |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-2e4524cf4357427785332fc9b9baf5a22025-01-29T13:36:39ZengWileyBrain and Behavior2162-32792025-01-01151n/an/a10.1002/brb3.70263Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian RandomizationLiumei Mo0Wei Pan1Wenjing Cao2Kui Wang3Li'an Huang4Department of NeurologyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdongChinaDepartment of CardiologyFoshan Women and Children HospitalFoshanGuangdongChinaDepartment of CardiologyFoshan Women and Children HospitalFoshanGuangdongChinaThe First Clinical Medical CollegeShandong UniversityJinan Shandong ChinaDepartment of NeurologyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdongChinaABSTRACT Background The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse immune cells and ICH using Mendelian randomization (MR) analysis. Methods Genetic variants associated with 731 immune cell traits were sourced from a comprehensive genome‐wide association study (GWAS) involving 3757 participants. Summary statistics data for ICH were acquired from FinnGen, comprising 4056 ICH cases and 371,717 controls. The principal analytical tool utilized in our study was the inverse‐variance weighted (IVW) method, incorporated as a key component of a two‐sample MR approach. To mitigate potential biases and verify the stability of the conclusions drawn from the primary analytical methods, a series of sensitivity analyses were performed. Results MR analysis elucidated 33 immune cell traits with causal associations, comprising B cells (eight traits), conventional dendritic cells (cDC, two traits), maturation stages of T cells (two traits), monocytes (two traits), myeloid cells (five traits), TBNK cells (six traits), and regulatory T cells (Treg, eight traits). DP (CD4+CD8+) %T cell (OR = 0.83, CI = 0.72–0.96, p = 0.013) exhibited the strongest protective effect. In contrast, transitional AC (OR = 1.09, CI = 1.02–1.16, p = 0.006) and IgD− CD27− %lymphocyte (OR = 1.08, CI = 1.00–1.17, p = 0.045) showed a higher tendency to increase the ICH risk. The sensitivity analyses validated the robustness and consistency of these results. Conclusion Our research provides robust evidence substantiating the causal relationship between specific immunophenotypes and ICH risk. The identification of these findings significantly enhances our understanding of the pathogenic mechanisms underlying ICH, particularly pertaining to the immune system. This breakthrough paves the way for innovative clinical and pharmaceutical research opportunities, potentially promoting the development of targeted therapies and enhanced strategies for managing and preventing ICH.https://doi.org/10.1002/brb3.70263genetic variantsgenome‐wide association studyimmune cellsintracerebral hemorrhageMR analyses |
| spellingShingle | Liumei Mo Wei Pan Wenjing Cao Kui Wang Li'an Huang Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization Brain and Behavior genetic variants genome‐wide association study immune cells intracerebral hemorrhage MR analyses |
| title | Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization |
| title_full | Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization |
| title_fullStr | Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization |
| title_full_unstemmed | Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization |
| title_short | Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization |
| title_sort | immune cells and intracerebral hemorrhage a causal investigation through mendelian randomization |
| topic | genetic variants genome‐wide association study immune cells intracerebral hemorrhage MR analyses |
| url | https://doi.org/10.1002/brb3.70263 |
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