ABSTRACT: Background: Epidemiological studies has investigated the correlation between ambient air pollution and neurosurgical multisystem diseases. Multiple studies have shown that air pollution significantly influences various neurological disorders. Nevertheless, the findings from these studies are inconsistent and contentious, leaving the causal relationships for many conditions unresolved. The study systematically investigates the underlying genetic causal relationships between air pollution and neurosurgical multisystem diseases, as well as to assess the implications of these associations. Methods: Genetic instruments for particulate matter (PM) with aerodynamic diameter < 2.5 μm (PM2.5), < 2.5-10 μm (PM2.5-10), <10 μm (PM10), PM2.5 absorbance, nitrogen dioxide (NO2), nitrogen oxides (NOx) and 30 neurosurgical multi-system diseases were selected. Results: In the European population, a noteworthy causal association was identified between NO2 and PM2.5 exposure and cerebral infarction (IVW: OR = 1.03, 95%CI: 1.01~1.06). Among African American or Afro-Caribbean individuals, NOx (IVW: OR = 0.63, 95%CI: 0.44~0.90) and NO2 (IVW: OR = 0.68, 95%CI: 0.54-0.87) are predisposed to trigger trigeminal neuralgia, while PM2.5 is related to 3 neurosurgical diseases, including epilepsy (IVW: OR = 0.89, 95%CI: 0.79~1.00), subarachnoid hemorrhage (IVW: OR = 0.75, 95%CI: 0.61~0.91), and diffuse brain injury (IVW: OR = 0.67, 95%CI: 0.47~0.96). In East Asian populations, a correlation has been observed between PM2.5 (IVW: OR = 0.99, 95%CI: 0.98~1.00) and PM10 (IVW: OR = 1.00, 95%CI: 1.00~1.00) exposure and the occurrence of cervical spondylosis. Additionally, there is a genetic susceptibility to pituitary adenoma and craniopharyngioma related to NO2 (IVW: OR = 1.24, 95%CI: 1.02~1.52) and PM2.5 absorbance (IVW: OR = 0.73, 95%CI: 0.59~0.90). In South Asian populations, there is a significant genetic susceptibility to the influences of PM2.5-10 (IVW: OR = 0.90, 95%CI: 0.83~0.97) on stroke incidence. In contrast, for populations in the Greater Middle East, air pollution is predominantly associated with cerebrovascular diseases. For example, PM2.5-10 shows a positive genetic predisposition towards stroke (IVW: OR = 1.02, 95%CI: 1.00~1.05) and subarachnoid hemorrhage (IVW: OR = 1.06, 95%CI: 1.00~1.12). Conclusion: This study presents the first genetic evidence establishing a connection between air pollution and neurosurgical multisystem diseases. Our findings emphasize the importance of air quality in the context of these diseases, potentially offering new insights into the underlying mechanisms and informing future clinical research on air pollution-mediated neurosurgical conditions, particularly cerebrovascular and brain functional disorders.
