Abstract
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.
Highlights
Alzheimer’s disease (AD) is a genetically complex multifactorial neurodegenerative disorder and can be regarded as the most common type of dementia, defined by extensive neuronal and synapses loss, the formation of extracellular amyloid-β (Aβ) plaques as well as the accumulation of intracellular neurofibrillary tangles (NFTs) in the brain [1]
The possession of at least one apolipoprotein E (APOE) ε4 allele was confirmed to increase the risk of developing late-onset AD (LOAD) (OR = 2.451, 95%confidence intervals (CIs) = 1.995–3.011, P < 0.001)
Based on the minor allele (C) frequency in controls, our sample size had more than 95% power to detect the odds ratios (ORs) of 0.78 for LOAD between carriers and no-carriers, at a significance level of 0.05
Summary
Alzheimer’s disease (AD) is a genetically complex multifactorial neurodegenerative disorder and can be regarded as the most common type of dementia, defined by extensive neuronal and synapses loss, the formation of extracellular amyloid-β (Aβ) plaques as well as the accumulation of intracellular neurofibrillary tangles (NFTs) in the brain [1]. Previous studies identified that multiple rare mutations in the APP, PSEN1, and PSEN2 genes contributes to early-onset familial AD. Only the ε4 allele of the apolipoprotein E (APOE) gene increases the risk of late-onset AD (LOAD). APOE only contributes to approximately 20% of LOAD risk, suggesting that numerous additional AD risk loci have not been identified so far. Previous GWAS identified some other genomic regions associated with LOAD, including CLU, PICALM, CR1, BIN1, MS4A, CD2AP, CD33, EPHA1, ABCA7, TREM2, etc. Previous GWAS identified some other genomic regions associated with LOAD, including CLU, PICALM, CR1, BIN1, MS4A, CD2AP, CD33, EPHA1, ABCA7, TREM2, etc. [3,4,5,6,7,8,9,10]
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