ZCWPW1 is associated with late-onset Alzheimer's disease in Han Chinese: a replication study and meta-analyses

Recently, a large genome-wide association study (GWAS) has identified a novel variant (rs1476679) within ZCWPW1 showing strong association with late-onset Alzheimer's disease (LOAD) in Caucasian. However, the effect of rs1476679 on other populations remains unclear. In order to explore whether rs1476679 is also associated with the LOAD risk in other ethnic groups, we recruited 2350 unrelated Northern Han Chinese subjects, which include 992 LOAD patients and 1358 healthy controls. Analysis of data from these subjects suggests that the rs1476679 polymorphism is significantly associated with the LOAD (genotype P = 0.017, allele P = 0.044). The logistic regression reveals the C allele at rs1476679 is a protective factor for LOAD in the dominant model (OR = 0.779, 95%CI = 0.659-0.921, Pc = 0.009) adjusting for gender, age and APOE ε4 status. Furthermore, rs1476679 can decrease the AD risk (Dominant: OR = 0.733, 95%CI = 0.607-0.884, Pc = 0.006; Additive: OR = 0.820, 95%CI = 0.708-0.950, Pc = 0.048) in APOE ε4 non-carriers after stratification. Furthermore, meta-analysis of 82525 individuals confirmed that rs1476679 within ZCWPW1 decreased the risk of LOAD (OR = 0.91, 95%CI = 0.89-0.94). To summarize, the rs1476679 polymorphism in ZCWPW1 is associated with LOAD in Northern Han Chinese population.