Dataset Information

Causal role of immune cells in alopecia areata: A two-sample Mendelian randomization study.

ABSTRACT:

Background

Previous research has highlighted an association between alopecia areata (AA) and the collapse of hair follicle immune privilege, however, the causal linkage to specific immune cell traits remains to be elucidated. This study aimed to investigate the causal influence of immune cell traits on AA utilizing a two-sample Mendelian randomization (MR) approach.

Methods

Leveraging GWAS summary statistics of 731 immunological traits (n = 3757) and AA data (n = 211,428), MR analyses were conducted employing inverse-variance weighted (IVW), weighted median, and MR-Egger regression methodologies. Sensitivity analyses were undertaken using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO analysis. A reverse MR analysis was performed for immune cell traits identified in the initial MR analysis.

Results

Our study unveiled multiple immune traits associated with AA. Protective associations were observed for CD62L- CD86+ myeloid dendritic cells (DCs), TD CD4+%CD4+ T cells, and others, with ORs ranging from 0.63 to 0.78. Conversely, traits like CD62L on CD62L+ plasmacytoid DCs, HLA-DR on CD14- CD16+ monocytes, HLA-DR on monocytes, and others, were determined to augment the risk of AA, with ORs ranging from 1.13 to 1.46. Reverse MR analysis signified a reduction in BAFF-R on IgD-CD24-B cells post-AA onset (OR: 0.97, 95% CI: 0.95-1.00), with no identified heterogeneity or horizontal pleiotropy among the instrumental variables (IVs).

Conclusions

Our findings suggests that CD62L on certain subpopulations of DCs and HLA-DR on monocytes may epitomize risk factors for AA, offering potential therapeutic targets for alleviating AA.

SUBMITTER: Xu W

PROVIDER: S-EPMC10788640 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Causal role of immune cells in alopecia areata: A two-sample Mendelian randomization study.

Xu Wen W Shen Yuqing Y Sun Jiayi J Wei Dongfan D Xie Bo B Song Xiuzu X

Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 20240101 1

<h4>Background</h4>Previous research has highlighted an association between alopecia areata (AA) and the collapse of hair follicle immune privilege, however, the causal linkage to specific immune cell traits remains to be elucidated. This study aimed to investigate the causal influence of immune cell traits on AA utilizing a two-sample Mendelian randomization (MR) approach.<h4>Methods</h4>Leveraging GWAS summary statistics of 731 immunological traits (n = 3757) and AA data (n = 211,428), MR anal ...[more]

PMID: 38221794

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Project description:BackgroundPrevious studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored.MethodsWe applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR-Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and identified immunophenotypes, using R software for all statistical calculations.ResultsOur MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (P<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (ORIVW =0.885; 95% CI: 0.798-0.983; P IVW =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (ORIVW =1.054; 95% CI: 1.010-1.100; P IVW =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (ORIVW =0.941; 95% CI: 0.898-0.987; P IVW =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) as well as on plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) in lung squamous cell carcinoma.ConclusionThis study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management.

Dataset Information

Causal role of immune cells in alopecia areata: A two-sample Mendelian randomization study.

Background

Methods

Results

Conclusions

Publications

Causal role of immune cells in alopecia areata: A two-sample Mendelian randomization study.

Similar Datasets

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