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

Alzheimer's & Dementia - Tập 9 - Trang 546-553 - 2013
Lan Tan1, Jin-Tai Yu1, Wei Zhang1, Zhong-Chen Wu1, Qun Zhang1, Qiu-Yan Liu1, Wei Wang1, Hui-Fu Wang1, Xiao-Ying Ma1, Wei-Zhen Cui2
1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, PR China
2Department of Gerontology, Qingdao Mental Health Center, Qingdao, PR China

Tóm tắt

AbstractObjectiveFive 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.MethodsWe 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.ResultsIn 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.ConclusionsThis 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.

Tài liệu tham khảo

10.1001/archneur.60.8.1119 10.1016/j.jalz.2011.02.004 10.1001/archneur.65.3.329 10.1001/archpsyc.63.2.168 10.3233/JAD-2002-4307 10.1038/ng.440 10.1038/ng.439 10.1001/jama.2010.574 10.1038/ng.803 10.1038/ng.801 10.1001/archneurol.2010.147 10.1001/archneurol.2010.201 10.1001/archgenpsychiatry.2010.196 10.1001/archneurol.2010.292 10.1038/ng.305 10.1016/j.neuron.2007.05.022 10.1016/j.neurobiolaging.2010.11.022 10.1001/archneurol.2010.108 10.1016/j.cca.2010.06.013 10.1016/j.brainres.2010.06.018 10.1016/j.jns.2010.09.027 10.1212/WNL.34.7.939 10.1038/75452 10.1016/j.hepres.2005.12.007 Terwilliger J, 1994, Handbook of human genetic linkage 10.1080/01621459.1995.10476572 10.1002/gepi.20217 10.1093/bioinformatics/19.1.149 10.1038/nrg2344 10.1007/s002510100339 10.1371/journal.pone.0009369 10.1038/nri2056 10.1016/j.ajhg.2008.10.008 10.1128/MCB.00383-07 10.2174/156720511795256080 10.1126/science.1072545 10.1186/1750-1326-6-54 10.1086/512133 Allen M, 2012, Association and heterogeneity at the GAPDH locus in Alzheimer's disease, Neurobiol Aging., 33, 203, 10.1016/j.neurobiolaging.2010.08.002 10.1001/jama.1997.03550160069041 10.1001/jama.299.11.1335 10.1097/EDE.0b013e318181b865 10.1001/archneurol.2008.552
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Alzheimer's & Dementia

Tập 9

546-553

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