Open AccessAssociation of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort
Author(s) -
Weiwei Li,
Zhen Wang,
Dong-Yu Fan,
Yujie Shen,
DongWan Chen,
Huiyun Li,
Ling Li,
Heng Yang,
Yuhui Liu,
XianLe Bu,
Wang-Sheng Jin,
Fan Zeng,
ZhiQiang Xu,
JinTai Yu,
LiYong Chen,
Yanjiang Wang
Publication year - 2020
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-020-00469-8
Subject(s) - single nucleotide polymorphism , medicine , genome wide association study , receiver operating characteristic , cohort , genetic association , disease , oncology , allele , genetics , genotype , biology , gene
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.