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Association of the Polygenic Risk Score with the Incidence Risk of Parkinson’s Disease and Cerebrospinal Fluid α-Synuclein in a Chinese Cohort

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Abstract

Parkinson’s disease (PD) is attributed to interactions among genes and environmental and lifestyle factors, but the genetic architecture of PD is complex and not completely understood. To evaluate whether the genetic profile modifies PD development and cerebrospinal fluid (CSF) pathological biomarkers, we enrolled 418 PD patients and 426 age- and sex-matched normal controls. Forty-six single nucleotide polymorphisms (SNPs) that were reported to be significantly associated with PD in large-scale genome-wide association studies (GWASs) were genotyped and analysed. The alleles associated with PD were used to build polygenic risk score (PRS) models to represent polygenic risk. The Cox proportional hazards model and receiver operating characteristic (ROC) analyses were used to evaluate the prediction value of the PRS for PD risk and age at onset. The CSF α-synuclein levels were measured in a subgroup of control subjects (n = 262), and its relationship with the PRS was analysed. We found that some SNPs identified from other populations had significant correlations with PD in our Chinese cohort. The PRS we built had prediction value for PD risk and age at onset. The CSF α-synuclein level had no correlation with the PRS in normal subjects.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Chinese Ministry of Science and Technology (grant no. 2016YFC1306401).

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Correspondence to Zhi-Qiang Xu or Yan-Jiang Wang.

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This study was approved by the Institutional Review Board of Daping Hospital, and all subjects and their caregivers provided informed consent.

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The authors declare that they have no competing interests.

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Li, WW., Fan, DY., Shen, YY. et al. Association of the Polygenic Risk Score with the Incidence Risk of Parkinson’s Disease and Cerebrospinal Fluid α-Synuclein in a Chinese Cohort. Neurotox Res 36, 515–522 (2019). https://doi.org/10.1007/s12640-019-00066-2

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  • DOI: https://doi.org/10.1007/s12640-019-00066-2

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