Shen Ting, Pu Jia-Li, Jiang Ya-Si, Yue Yu-Mei, He Ting-Ting, Qu Bo-Yi, Zhao Shuai, Yan Ya-Ping, Lai Hsin-Yi, Zhang Bao-Rong
Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; Department of Neurology of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Neural Regen Res. 2023 May;18(5):1154-1160. doi: 10.4103/1673-5374.355764.
Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson's disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease. Forty-eight Parkinson's disease patients and 39 matched healthy controls underwent genotyping and 7T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson's disease diagnosis. We found that, in Parkinson's disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein (SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson's disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson's disease.
多个单核苷酸多态性可能导致帕金森病的认知功能衰退。然而，这些单核苷酸多态性改变脑成像表型的机制仍不清楚。本研究的目的是调查多个单核苷酸多态性对帕金森病脑成像表型的潜在影响。48例帕金森病患者和39例匹配的健康对照者接受了基因分型和7T磁共振成像检查。设计了一个认知加权多基因风险评分模型，其中分别确定了36个单核苷酸多态性的效应大小。分析了多基因风险评分、神经影像学特征和临床数据之间的相关性。此外，进行了个体单核苷酸多态性分析，以探讨基因型的主要效应及其与帕金森病诊断的交互效应。我们发现，在帕金森病中，多基因风险评分与海马体、海马旁回和梭状回的神经活动相关，与海马-前额叶和梭状回-颞叶的连接性相关，也与眶额皮质的灰质改变相关。此外，我们发现α-突触核蛋白（SNCA）中的单核苷酸多态性与放射冠上部、胼胝体和外囊的白质微观结构变化相关。儿茶酚-O-甲基转移酶中的一个单核苷酸多态性与参与视觉认知功能障碍的舌回、梭状回和枕叶的神经活动相关。此外多巴胺受体D3（DRD3）与额叶和颞叶的功能及结构相关。总之，影像遗传学有助于更好地理解帕金森病病理生理过程中涉及的遗传途径。本研究提供了帕金森病中遗传因素、认知功能和多模态神经影像学生物标志物之间存在关联的证据。
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