An association study of Alzheimer’s disease risk genes in a Chinese population

Abstract

AbstractBackgroundGenome‐wide association studies (GWAS) and whole‐exome sequencing have identified a number of risk genes playing a significant role in the pathogenesis of Alzheimer’s disease (AD). However, most of the genetic studies are from Caucasian populations and relatively rare in Chinese population.MethodWe sequenced 33 AD risk genes using Targeted panel sequencing in 721 AD patients and 365 normal controls in Han population of Southern China. A series of bioinformatic methods including common‐variant (0.01≤MAF≤0.5) based association analysis and gene‐based association analysis on rare variants (MAF<0.01) were performed between AD patients and normal controls.ResultWe identified nine common variants with significant differences, three of them had been reported, including rs429358 in APOE, rs4147929 in ABCA7 and rs3752246 in ABCA7, while other six variants were novel, including rs3752229 in ABCA7, rs4147935 in ABCA7, rs17125497 in SORL1, rs2282647 in SORL1, rs11218355 in SORL1, and rs11682128 in BIN1. The area under the ROC (AUC) of the nine significant loci model was 0.670. Gene‐based association analysis on rare variants showed that the p value of RIN3 was less than 0.05 both in the Sequence Kernel Association Test‐Optimal (SKAT‐O) test and logistic regression analysis (age, gender and APOE ε4 as covariates) between AD patients and normal controls (p = 0.0399, corrected P = 0.0346).ConclusionWe conclude that APOE, ABCA7, SORL1, BIN1 and RIN3 are risk factors for AD in Chinese population.