Genetic architecture of Parkinson's disease: investigating the relationships between pathway‐specific polygenic risk scores and neuroanatomical features

Our findings reveal a link between PD genetic risk and brain structure, indicative of greater size of grey matter and higher white matter integrity, potentially leading to increased risk of PD development. Additionally, the lower expression of mitochondrial and autophagy pathway genes during fetal stages as well as the non-significant associations between pathway-specific polygenic risk scores and neuroanatomical features suggest that these pathways may contribute to disease risk through mechanisms independent of early neurodevelopmental processes. These results provide new insights into how genetic risk factors might shape brain structure and contribute to PD susceptibility, highlighting the complex interplay between developmental and pathway-specific mechanisms in PD pathogenesis.