Genome-wide association assessment between immune cells and osteoarthritis: a bidirectional Mendelian randomization...

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• The immune microenvironment is crucial in osteoarthritis (OA) development, but prior research on immune cell involvement yielded inconsistent findings.
• Understanding the precise causal relationships between immune cell traits and OA is essential for developing effective treatments.

Purpose of the Study:

• To investigate the causal association between various immune cell traits and osteoarthritis (OA) using a bidirectional Mendelian randomization approach.
• To identify specific immune cell phenotypes that causally influence OA pathogenesis.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis integrating large-scale genome-wide association studies (GWAS) for OA and 731 immune phenotypes.
• Inverse variance weighted (IVW) method for primary causal effect estimation, supported by MR Egger, weighted median, and mode-based methods.
• Sensitivity analyses (MR Egger, leave-one-out) and replication analysis in an independent cohort to ensure robustness and validate findings.

Main Results:

• Thirteen immune cell traits demonstrated significant causal relationships with OA after FDR correction, including B cells, conventional dendritic cells (cDCs), monocytes, and T, B, and NK cells (TBNK).
• The strongest associations were observed for "CD64 on CD14- CD16+ monocyte" and "CD16+ monocyte %monocyte", with replication confirming the effect of "CD64 on CD14- CD16+ monocyte" and "HLA DR+ NK %NK" on OA.
• No significant heterogeneity or horizontal pleiotropy was detected, and five immune traits were found to be influenced by OA.

Conclusions:

• This study establishes causal links between specific immune cell traits and OA, providing genetic evidence for the role of immune cells in OA pathogenesis.
• The findings highlight potential immunological targets for novel OA treatments and deepen our understanding of OA etiology.