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Association of GWAS‐linked loci with late‐onset Alzheimer's disease in a northern Han Chinese population
Author(s) -
Tan Lan,
Yu JinTai,
Zhang Wei,
Wu ZhongChen,
Zhang Qun,
Liu QiuYan,
Wang Wei,
Wang HuiFu,
Ma XiaoYing,
Cui WeiZhen
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.08.007
Subject(s) - genome wide association study , apolipoprotein e , bonferroni correction , odds ratio , single nucleotide polymorphism , genetic association , population , allele , genetics , biology , medicine , oncology , genotype , disease , gene , statistics , mathematics , environmental health
Objective Five genomewide association studies (GWAS) in white populations have recently identified and confirmed 9 novel Alzheimer's disease (AD) susceptibility loci ( CLU , CR1 , PICALM, BIN1 , ABCA7 , MS4A gene cluster, CD2AP , CD33, and EPHA1 ). These studies have been conducted almost exclusively in white populations and it is unclear whether these observations generalize to populations with different ethnicities. Methods We recruited 1224 unrelated northern Han Chinese subjects comprising 612 patients with a clinical diagnosis of late‐onset AD (LOAD) according to the criteria of the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association and 612 healthy age‐ and sex‐matched control subjects. Because of our previous study investigating CLU, CR1, and PICALM in the Han population, we limited the current analysis to BIN1 , ABCA7 , MS4A gene cluster, CD2AP , CD33 , and EPHA1 . Results In a multivariate analysis, associations of MS4A6A (rs610932; odds ratio = 0.632, Bonferroni corrected P = .019) and CD33 (rs3865444; odds ratio = 1.492, Bonferroni corrected P = .017) with LOAD were replicated successfully. When these data were stratified by apolipoprotein E ( APOE ) ε4 status, both rs610932 and rs610932 were evident only among subjects without the APOE ε4 allele. For BIN1 , assuming a dominant model of inheritance, a positive association for rs7561528 in APOE ε4 carriers was observed. This association, however, did not remain significant after Bonferroni correction. As for ABCA7 , CD2AP, and EPHA1 single nucleotide polymorphisms from recent GWAS, despite the similar directional effects, no significant differences in genotype and estimated allele frequency distribution between patients and control subjects were observed. Conclusions This study provides the first independent evidence that MS4A and CD33 loci are associated with the risk of LOAD in northern Han Chinese population. Genotypes at the two loci confer risk predominantly in APOE ε4‐negative subjects.