Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1154;epage=1160;aulast=Shen |
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| author | Ting Shen Jia-Li Pu Ya-Si Jiang Yu-Mei Yue Ting-Ting He Bo-Yi Qu Shuai Zhao Ya-Ping Yan Hsin-Yi Lai Bao-Rong Zhang |
| author_facet | Ting Shen Jia-Li Pu Ya-Si Jiang Yu-Mei Yue Ting-Ting He Bo-Yi Qu Shuai Zhao Ya-Ping Yan Hsin-Yi Lai Bao-Rong Zhang |
| author_sort | Ting Shen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:42:52Z |
| format | Article |
| id | doaj.art-00cddb63b0cd4e5cbd8388ce1b393c70 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-12T07:42:52Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-00cddb63b0cd4e5cbd8388ce1b393c702022-12-22T03:41:47ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011851154116010.4103/1673-5374.355764Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s diseaseTing ShenJia-Li PuYa-Si JiangYu-Mei YueTing-Ting HeBo-Yi QuShuai ZhaoYa-Ping YanHsin-Yi LaiBao-Rong ZhangMultiple 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1154;epage=1160;aulast=Shencognition; imaging genetics; magnetic resonance imaging; multi-modality; parkinson’s disease; polygenic risk score; single nucleotide polymorphism; ultra-high field |
| spellingShingle | Ting Shen Jia-Li Pu Ya-Si Jiang Yu-Mei Yue Ting-Ting He Bo-Yi Qu Shuai Zhao Ya-Ping Yan Hsin-Yi Lai Bao-Rong Zhang Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease Neural Regeneration Research cognition; imaging genetics; magnetic resonance imaging; multi-modality; parkinson’s disease; polygenic risk score; single nucleotide polymorphism; ultra-high field |
| title | Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease |
| title_full | Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease |
| title_fullStr | Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease |
| title_full_unstemmed | Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease |
| title_short | Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease |
| title_sort | impact of cognition related single nucleotide polymorphisms on brain imaging phenotype in parkinson s disease |
| topic | cognition; imaging genetics; magnetic resonance imaging; multi-modality; parkinson’s disease; polygenic risk score; single nucleotide polymorphism; ultra-high field |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=5;spage=1154;epage=1160;aulast=Shen |
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