Research Papers: Gerotarget (Focus on Aging):

Association and interaction effects of Alzheimer’s disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population

Eugene Lin _, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C. Yang and Chung-Feng Kao

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Oncotarget. 2017; 8:24077-24087. https://doi.org/10.18632/oncotarget.15269

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Eugene Lin1,2,3,*, Shih-Jen Tsai4,5,*, Po-Hsiu Kuo6, Yu-Li Liu7, Albert C. Yang4,5 and Chung-Feng Kao8

1 Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

2 Vita Genomics, Inc., Taipei, Taiwan

3 TickleFish Systems Corporation, Seattle, WA, USA

4 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

5 Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan

6 Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan

7 Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan

8 Department of Agronomy, College of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan

* These authors have contributed equally to this work

Correspondence to:

Eugene Lin, email:

Shih-Jen Tsai, email:

Keywords: Alzheimer’s diseases; cognitive aging; gene-gene and gene-lifestyle interactions; Mini-Mental State Examination; single nucleotide polymorphisms; Gerotarget

Received: October 17, 2016 Accepted: January 29, 2017 Published: February 11, 2017


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.

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