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To comprehensively characterize the gray matter volume alterations in PD patients, we conducted a neuroimaging meta-analysis and validated the observed atrophic phenotypes in an independent dataset. Leveraging the Allen Human Brain Atlas (AHBA), we linked brain transcriptomic data to neuroimaging phenotypes to identify genes associated with PD-related gray matter atrophy. Further enrichment analyses and functional characterization explored the potential roles of these correlated genes in disease pathology. Both the neuroimaging meta-analysis and independent dataset analysis consistently revealed significant gray matter atrophy in PD, particularly in the superior temporal gyrus, highly associated with sensory and motor functions. Spatial transcriptome-neuroimaging correlation analysis identified 1,952 overlapping genes whose expression levels were significantly correlated with the spatial distribution of gray matter atrophy in PD patients. These genes were enriched in several key biological processes and molecular pathways, exhibiting region- and cell type-specific expression, particularly in dopaminergic receptor neurons of brain tissue. This study delineates the spatial distribution of gray matter atrophy in PD and suggests that this neurodegenerative phenotype may result from complex interactions among multiple functionally relevant genes.<\/jats:p>","DOI":"10.1093\/cercor\/bhaf097","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:14:41Z","timestamp":1745997281000},"source":"Crossref","is-referenced-by-count":4,"title":["Genetic mechanisms underlying gray matter atrophy in Parkinson\u2019s disease: a combined transcriptome and neuroimaging study"],"prefix":"10.1093","volume":"35","author":[{"given":"Yi","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Radiology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University , No. 299, Qingyang Road, Wuxi City 214023, Jiangsu Province,","place":["China"]},{"name":"Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University , No. 299, Qingyang Road, Wuxi City 214023, Jiangsu 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