title: Association and interaction effects of Alzheimer's disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population.
abstract: Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the ABCA7, APOE, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB1, HLA-DRB4, INPP5D, MEF2C, MS4A4A, MS4A4E, MS4A6E, NME8, PICALM, PLD3, PTK2B, RIN3, SLC24A4, SORL1, and ZCWPW1 genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. We also analyzed the interactions between lifestyle and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to evaluate cognitive functions. Out of the 588 SNPs tested in this study, only the association between CASS4-rs911159 and cognitive aging persisted significantly (P = 2.2 x 10-5) after Bonferroni correction. Our data also showed a nominal association of cognitive aging with the SNPs in six more key AD-associated genes, including EPHA1-rs10952552, FERMT2-rs4901317, MEF2C-rs9293506, PLD3-rs11672825, RIN3-rs1885747, and SLC24A4-rs67063100 (P = 0.0018~0.0097). Additionally, we found the interactions among CASS4-rs911159, EPHA-rs10952552, FERMT2-rs4901317, MEF2C-rs9293506, or SLC24A4-rs67063100 on cognitive aging (P = 0.004~0.035). Moreover, our analysis suggested the interactions of SLC24A4-rs67063100 or MEF2C-rs9293506 with lifestyle such as alcohol consumption, smoking status, physical activity, or social support on cognitive aging (P = 0.008~0.041). Our study indicates that the AD-associated genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-lifestyle interactions.
authors.affiliation: Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.|Vita Genomics, Inc., Taipei, Taiwan.|TickleFish Systems Corporation, Seattle, WA, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.affiliation: Department of Agronomy, College of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Kao
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D000066492:Cognitive Aging / Q000523:psychology*; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
keywords: Alzheimer’s diseases; Gerotarget; Mini-Mental State Examination; cognitive aging; gene-gene and gene-lifestyle interactions; single nucleotide polymorphisms