Genetic mechanisms underlying gray matter atrophy in Parkinson’s disease: a combined transcriptome and neuroimaging study

Motivation: Extensive research has shown prominent gray matter atrophy in patients with Parkinson's disease, yet its genetic mechanisms are largely unknown. Goal(s): We aimed to investigate the genetic mechanisms underlying gray matter atrophy in PD. Approach: We performed a comprehensive neuroimaging meta-analysis along with an independent dataset analysis. Utilizing the Allen Human Brain Atlas, we performed spatial association analyses linking transcriptome data to neuroimaging findings, along with gene functional feature analyses for the identified genes. Results: Our findings suggest that prominent gray matter atrophy in PD may be a consequence of intricate interactions among a diverse set of genes with various functional features. Impact: Our findings may offer unique insights into the genetic mechanisms underlying brain gray matter atrophy in Parkinson’s Disease through bridging the gap between microscale molecular function and macroscale brain architecture.