Exploring the causal relationship and pathogenesis of intracranial aneurysms with osteoporosis based on Mendelian...

Intracranial aneurysms (IA) and osteoporosis (OP) are both common conditions among the elderly population. Observational studies suggest a potential association between OP and IA. However, the causal relationships and biological mechanisms underlying these associations remain unclear.

We performed bidirectional two-sample Mendelian randomization (TSMR) analysis using summary statistics from European genome-wide association studies. The inverse variance weighted (IVW) method served as the primary approach for causal inference. Furthermore, sensitivity analyses were conducted to evaluate the potential level of heterogeneity and horizontal pleiotropy, thereby demonstrating the robustness of the findings. Subsequent bioinformatics analysis employed machine learning algorithms to identify potential OP-related diagnostic biomarkers in IA, with diagnostic performance assessed using receiver operating characteristic curves. Furthermore, immune infiltration analysis was performed to preliminarily characterize the immune microenvironment features in IA patients.

IVW results suggested a potential association between low bone density and an increased risk of IA, although this finding did not remain significant after correction for multiple testing. Reverse Mendelian randomization (MR) analysis revealed that the genetic susceptibility to IA did not have a significant impact on the relative risk of bone density. Furthermore, our study identified 5 potential OP-related biomarkers in IA, which showed valuable diagnostic performance. Immune cell infiltration analysis suggested that the formation of IA may be related to immune responses induced by CD8 T cells, macrophages, and mast cells.

These findings provide valuable insights into the relationship between OP and IA, offering new perspectives for the diagnosis and treatment of IA.