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

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).

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.

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.