Researching the causal relationship between immune cells and frontotemporal Dementia: A Mendelian Randomization analysis

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-04-02 DOI:10.1016/j.brainres.2025.149608

Yueming Cheng , Xia He , Xialian Huang , Fengle Mao , Fuli Qin , Yanqiu Wang

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引用次数: 0

Abstract

Background

Frontotemporal dementia (FTD) is a prevalent dementia syndrome with poorly understood immunological underpinnings. Despite the widespread adoption of high-density genotyping technologies like SNPs and CNVs, and advances in genome-wide association studies (GWAS), the immunological mechanisms underlying FTD remain elusive. This study aims to elucidate the causal relationships between immune cell traits and FTD using Mendelian randomization (MR).

Methods

We utilized summary data for FTD (cases = 129, controls = 392,463) from the FinnGen dataset and summary statistics for 731 immune cell traits from the GWAS catalog. These traits included morphological parameters (MP = 32), median fluorescence intensity (MFI = 389), absolute cell counts (AC = 118), and relative cell counts (RC = 192). Our approach encompassed forward MR (immune cell traits as exposure) and reverse MR (FTD as exposure), accompanied by rigorous sensitivity analyses to assess the robustness and heterogeneity of the findings.

Results

FTD did not have a statistically significant impact on immune phenotypes. Notably, we identified 13 immune phenotypes as protective against FTD, including various T cell and B cell markers. Conversely, 8 phenotypes were associated with increased FTD risk, involving markers on myeloid cells and subsets of T and B cells;

Conclusion

This MR study identifies specific immune phenotypes associated with FTD, highlighting potential pathways for future clinical research and therapeutic intervention.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.