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

被引：32

作者：

Lin, Eugene ^{[1
,2
,3
]}

Tsai, Shih-Jen ^{[4
,5
]}

Kuo, Po-Hsiu ^{[6
]}

Liu, Yu-Li ^{[7
]}

Yang, Albert C. ^{[4
,5
]}

Kao, Chung-Feng ^{[8
]}

机构：

[1] China Med Univ, Inst Biomed Sci, Taichung, Taiwan

[2] Vita Genom Inc, Taipei, Taiwan

[3] TickleFish Syst Corp, Seattle, WA 98115 USA

[4] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan

[5] Natl Yang Ming Univ, Div Psychiat, Taipei, Taiwan

[6] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Dept Publ Hlth, Taipei, Taiwan

[7] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Zhunan Township, Miaoli County, Taiwan

[8] Natl Chung Hsing Univ, Coll Agr & Nat Resources, Dept Agron, Taichung, Taiwan

来源：

ONCOTARGET | 2017年 / 8卷 / 15期

关键词：

Alzheimer's diseases; cognitive aging; gene-gene and gene-lifestyle interactions; Mini-Mental State Examination; single nucleotide polymorphisms; Gerotarget; GENOME-WIDE ASSOCIATION; METABOLIC PHENOTYPES; IDENTIFIES VARIANTS; COMMON VARIANTS; OBESITY; RISK; POLYMORPHISM; LOCI; CLU; SORL1;

D O I：

10.18632/oncotarget.15269

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-associated genes 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 similar to 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 similar to 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 similar to 0.041). Our study indicates that the AD-associated genes may contribute to the risk of cognitive aging independently as well as through genegene and gene-lifestyle interactions.

引用

页码：24077 / 24087

页数：11

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