An exploratory Mendelian randomization study on the genetically predicted effects of circulating blood cells on...

The causal relationship between circulating blood cells and Osteoarthritis (OA) remains unclear. This study aimed to explore this potential relationship using a two-sample Mendelian Randomization (MR) approach.

Data from large-scale GWAS (Blood Cell Consortium and GWAS Catalog) were analyzed using two-sample MR methods, with Inverse Variance Weighting as the primary approach. A Bonferroni correction was applied for multiple testing for the two primary traits. Robustness was assessed through comprehensive sensitivity analyses for heterogeneity and pleiotropy.

After Bonferroni correction, Genetically Predicted Hemoglobin (HGB) showed a weak genetic association consistent with a potential causal pathway for OA risk (OR = 1.004, 95% CI 1.001-1.007, p = 0.018). The association for Neutrophil (NEU) count was not statistically significant. While sensitivity analyses did not detect directional pleiotropy, significant heterogeneity was observed for the genetic instruments.

This exploratory study provides preliminary genetic evidence for a statistically significant but clinically negligible MR estimate of hemoglobin in OA pathogenesis. The clinical and biological significance of this minuscule effect remains uncertain. The findings should be interpreted as hypothesis-generating, highlighting the need for further research rather than establishing a definitive causal link.