title: Influence of Alzheimer's disease genes on cognitive decline: the Guangzhou Biobank Cohort Study.
abstract: Cognitive decline is a reduction in cognitive ability usually associated with aging, and those with more extreme cognitive decline either have or are at risk of progressing to mild cognitive impairment and dementia including Alzheimer's disease (AD). We hypothesized that genetic variants predisposing to AD should be predictive of cognitive decline in elderly individuals. We selected 1325 subjects with extreme cognitive decline and 1083 well-matched control subjects from the Guangzhou Biobank Cohort Study in which more than 30,000 southern Chinese older people have been recruited and followed up. Thirty single-nucleotide polymorphisms in 29 AD-associated genes were genotyped. No statistically significant allelic associations with cognitive decline were found by individual variant analysis. At the level of genotypic association, we confirmed that the APOE ε4 homozygote significantly accelerated cognitive decline and found that carriers of the ACE rs1800764_C allele were more likely to show cognitive decline than noncarriers, particularly in those without college education. However, these effects do not survive after multiple testing corrections, and together they only explain 1.7% of the phenotypic variance in cognitive score change. This study suggests that AD risk variants and/or genes are not powerful predictors of cognitive decline in our Chinese sample.
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Gui
authors.affiliation: Guangzhou No. 12 Hospital, Guangzhou, China.
authors.forename: Chao Qiang
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China; Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. Electronic address: cherny@hku.hk.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China; Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Guangzhou No. 12 Hospital, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Guangzhou No. 12 Hospital, Guangzhou, China.
authors.forename: Ya Li
authors.initials: YL
authors.lastname: Jin
authors.affiliation: Guangzhou No. 12 Hospital, Guangzhou, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Guangzhou No. 12 Hospital, Guangzhou, China.
authors.forename: Wei Sen
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: Department of Public Health, Epidemiology, and Biostatistics, University of Birmingham, Birmingham, UK.
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.affiliation: Department of Public Health, Epidemiology, and Biostatistics, University of Birmingham, Birmingham, UK.
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D053327:Apolipoprotein E4; D007703:Peptidyl-Dipeptidase A
keywords: ACE; APOE; Alzheimer's disease; Cognitive decline; Joint effect