Investigating the shared genetic architecture between Parkinson's disease and magnetic susceptibility of the substantia nigra
Parkinson's disease (PD) is a common and progressively deteriorating neurodegenerative disorder thatprofoundly affects millions of individuals worldwide. Neuroimaging research has consistently demonstrated abnormalities in quantitative susceptibility mapping (QSM) within the substantia nigra (S...
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| Main Author: | |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-09-01
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| Series: | Meta-Radiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950162825000256 |
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| Summary: | Parkinson's disease (PD) is a common and progressively deteriorating neurodegenerative disorder thatprofoundly affects millions of individuals worldwide. Neuroimaging research has consistently demonstrated abnormalities in quantitative susceptibility mapping (QSM) within the substantia nigra (SN) that are associated with Parkinson's disease. However, the genetic underpinnings shared between Parkinson's disease and QSM of substantia nigra remain inadequately understood. Here, genetic pleiotropic analyses were conducted to explore genetic overlap at global, local, and variant levels byleveraging summary statistics from the largest genome-wide association studies for PD (N = 501,348) and QSM of SN (N = 35,273). We observed a significant global genetic correlation between PD and QSM of SN (rg = 0.096, p = 0.032 with LDSC; rg = 0.097, p = 0.048 with SumHer). Local-level analysis identified six genomic regions showing shared associations with the two traits. At the variant level, we found 12 genetic variants shared by PD and QSM of SN. These shared risk variants were mapped to 33 unique genes. We analyzed drug-gene interactions based on these shared genes and their associations with PD medications. These findings elucidate the genetic interplay between SN magnetic susceptibility and PD pathogenesis, revealing potential biomarker discovery and targets for therapeutic development. |
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| ISSN: | 2950-1628 |