Residential greenness, air pollution, and epilepsy: Insight in genetic susceptibility and life expectancy.

INTRODUCTION: Epilepsy is one of the most common neurological disorders worldwide, yet evidence on its environmental determinants remains limited. Although a few studies have linked air pollution to epilepsy onset, the potential influence of residential greenness has not been investigated. Moreover, whether genetic susceptibility modifies these associations remains unclear. OBJECTIVES: We aimed to examine the associations of residential greenness and air pollutants with incident epilepsy and to evaluate the modification effect of genetic susceptibility. We also assessed the relationship between environmental factors and life expectancy among people with epilepsy. METHODS: Residential greenness was quantified using the normalized difference vegetation index (NDVI) for 437,526 UK Biobank participants. Air pollution levels were estimated using land-use regression models. Polygenic risk scores (PRS) were calculated to assess genetic susceptibility to epilepsy. These relationships were examined using Cox models. Causal mediation analysis was employed to estimate the mediation effects. Furthermore, we calculated population attributable risk (PAR%) and life expectancy. RESULTS: Over a median follow-up of 11.78 years, 2,448 incident epilepsy were identified. Each interquartile-range increase in greenness was associated with a 7-8% lower risk of epilepsy, whereas air pollution was associated with a 5-9% higher risk. Additive and multiplicative interactions were observed between greenness and PRS (all SIs < 1; Pinteraction < 0.1), but not for air pollutants. PAR% for greenness and air pollutants ranged from 16.1% to 24.3%. PM2.5 mediated 38.26-48.38% of the association between greenness and epilepsy. Epileptics exposed to high greenness or low air pollution had 1.76-2.67 years longer life expectancy at age 45. Given the observational design, further studies are warranted to confirm these findings. CONCLUSIONS: Residential greenness and air pollutants were associated with epilepsy incidence and progression. Interactions between greenness and genetic susceptibility were observed. Mitigating air pollution and enhancing greenness may provide substantial neurological health benefits.