Lin Eugene, Tsai Shih-Jen, Kuo Po-Hsiu, Liu Yu-Li, Yang Albert C, Kao Chung-Feng
Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Vita Genomics, Inc., Taipei, Taiwan.
Oncotarget. 2017 Apr 11;8(15):24077-24087. doi: 10.18632/oncotarget.15269.
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 = 0.00180.0097). Additionally, we found the interactions among CASS4-rs911159, EPHA-rs10952552, FERMT2-rs4901317, MEF2C-rs9293506, or SLC24A4-rs67063100 on cognitive aging (P = 0.0040.035). 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.
全基因组关联研究及荟萃分析表明，患阿尔茨海默病（AD）风险的增加与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和ZCWPW1基因有关。在本研究中，我们评估了这27个与AD相关基因内的单核苷酸多态性（SNP）是否独立地和/或通过复杂的相互作用与台湾老年人群的认知衰老相关联。我们还分析了生活方式与这些基因在影响认知衰老方面的相互作用。对来自台湾生物银行的634名60岁以上的台湾受试者进行了分析。对所有受试者进行简易精神状态检查表（MMSE）评分以评估认知功能。在本研究中测试的588个SNP中，经Bonferroni校正后，只有CASS4 - rs911159与认知衰老之间的关联仍然显著（P = 2.2×10 - 5）显示名义上的关联。我们的数据还显示认知衰老与另外六个关键AD相关基因中的SNP之间存在名义上的关联，包括EPHA1 - rs10952552、FERMT2 - rs4901317、MEF2C - rs9293506、PLD3 - rs11672825、RIN3 - rs1885747和SLC24A4 - rs67063100（P = 0.0018至0.0097）。此外，我们发现CASS4 - rs911159、EPHA - rs10952552、FERMT2 - rs4901317、MEF2C - rs9293506或SLC24A4 - rs67063100之间在认知衰老方面存在相互作用（P = 0.004至0.035）。此外，我们的分析表明SLC24A4 - rs67063100或MEF2C - rs9293506与生活方式如饮酒、吸烟状况、体育活动或社会支持在认知衰老方面存在相互作用（P = 0.008至0.041）。我们的研究表明，与AD相关的基因可能独立地以及通过基因 - 基因和基因 - 生活方式的相互作用导致认知衰老的风险。
