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Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort

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Abstract

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

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Acknowledgements

We would like to thank the patients and their families for their participation and dedication to research. This work was supported by the National Basic Research Development Program of Ministry of Science and Technology of China (2016YFC1306401) and the National Natural Science Foundation of China (91749206).

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Author notes

  1. Wei-Wei Li and Zhen Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Wei-Wei Li, Dong-Yu Fan, Ying-Ying Shen, Dong-Wan Chen, Hui-Yun Li, Ling Li, Heng Yang, Yu-Hui Liu, Xian-Le Bu, Wang-Sheng Jin, Fan Zeng, Zhi-Qiang Xu & Yan-Jiang Wang

  2. Department of Anaesthesiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Zhen Wang & Li-Yong Chen

  3. Chongqing Key Laboratory of Aging and Diseases, Chongqing, 400042, China

    Yan-Jiang Wang

  4. Centre for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China

    Yan-Jiang Wang

  5. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Jin-Tai Yu

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  1. Wei-Wei Li
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Correspondence to Li-Yong Chen or Yan-Jiang Wang.

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Li, WW., Wang, Z., Fan, DY. et al. Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort. Neurosci. Bull. 36, 696–704 (2020). https://doi.org/10.1007/s12264-020-00469-8

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