Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (5): 1154-1160.doi: 10.4103/1673-5374.355764

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Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Ting Shen1, 2, #, Jia-Li Pu1, #, Ya-Si Jiang1, 2, Yu-Mei Yue3, Ting-Ting He2, 4, Bo-Yi Qu2, 4, Shuai Zhao1, Ya-Ping Yan1, Hsin-Yi Lai2, 3, 4, *, Bao-Rong Zhang1, *#br#   

  1. 1Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China;  2Department 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;  3Department of Neurology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China;  4College of Biomedical Engineering and Instrument Science, Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, Zhejiang Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Bao-Rong Zhang, MD, PhD, brzhang@zju.edu.cn; Hsin-Yi Lai, PhD, laihy@zju.edu.cn.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, Nos. 81771216 (to JLP), 81520108010 (to BRZ), and 82101323 (to TS), the National Key R&D Program of China, No. 2018YFA0701400 (to HYL), the Primary Research and Development Plan of Zhejiang Province, No. 2020C03020 (to BRZ), the Key Project of Zhejiang Laboratory, No. 2018EB0ZX01 (to HYL), the Fundamental Research Funds for the Central Universities, No. 2019XZZX001-01-21 (to HYL), and Preferred Foundation of Zhejiang Postdoctors, No. ZJ2021152 (to TS).

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Abstract: 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.

Key words: cognition, imaging genetics, magnetic resonance imaging, multi-modality, Parkinson’s disease, polygenic risk score, single nucleotide polymorphism, ultra-high field