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  • Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.

Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.

Mechanisms of ageing and development (2021-04-03)
Anatoliy I Yashin, Deqing Wu, Konstantin Arbeev, Olivia Bagley, Igor Akushevich, Matt Duan, Arseniy Yashkin, Svetlana Ukraintseva
摘要

Emerging evidence from experimental and clinical research suggests that stress-related genes may play key roles in AD development. The fact that genome-wide association studies were not able to detect a contribution of such genes to AD indicates the possibility that these genes may influence AD non-linearly, through interactions of their products. In this paper, we selected two stress-related genes (GCN2/EIF2AK4 and APP) based on recent findings from experimental studies which suggest that the interplay between these genes might influence AD in humans. To test this hypothesis, we evaluated the effects of interactions between SNPs in these two genes on AD occurrence, using the Health and Retirement Study data on white indidividuals. We found several interacting SNP-pairs whose associations with AD remained statistically significant after correction for multiple testing. These findings emphasize the importance of nonlinear mechanisms of polygenic AD regulation that cannot be detected in traditional association studies. To estimate collective effects of multiple interacting SNP-pairs on AD, we constructed a new composite index, called Interaction Polygenic Risk Score, and showed that its association with AD is highly statistically significant. These results open a new avenue in the analyses of mechanisms of complex multigenic AD regulation.

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淀粉样β-蛋白片段35-25, ≥95% (HPLC)
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5 g
国内现货,预计发货时间 April 08, 2025
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25 g
国内现货,预计发货时间 April 08, 2025
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CN¥6,630.66