Association of GWAS-linked loci with late-onset Alzheimer's disease in a northern Han Chinese population

作者：Tan, Lan^*; Yu, Jin-Tai; Zhang, Wei; Wu, Zhong-Chen; Zhang, Qun; Liu, Qiu-Yan; Wang, Wei; Wang, Hui-Fu; Ma, Xiao-Ying; Cui, Wei-Zhen

来源：Alzheimer's and Dementia, 2013, 9(5): 546-553.

DOI：10.1016/j.jalz.2012.08.007

• Alzheimer's disease
• Polymorphism
• MS4A
• CD33
• Genomewide association studies

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) epsilon 4 status, both rs610932 and rs610932 were evident only among subjects without the APOE epsilon 4 allele. For BIN1, assuming a dominant model of inheritance, a positive association for rs7561528 in APOE epsilon 4 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 epsilon 4-negative subjects.

• 出版日期2013-9
• 单位青岛大学; 青岛市市立医院; 上海市精神卫生中心