ArticleMechanisms of ageing and development2021
Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.
Article in Mechanisms of ageing and development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- GPCR-Mediated Cell Intelligence: A Potential Mechanism for Survival and Long-Term Health.Current issues in molecular biology · 2026Review
- Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.The Biochemical journal · 2024Article
- Understanding Alzheimer's disease in the context of aging: Findings from applications of stochastic process models to the Health and Retirement Study.Mechanisms of ageing and development · 2023Article
- Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.Journal of translational genetics and genomics · 2021Article
- Expanding the scope of health disparities research in Alzheimer's disease and related dementias: Recommendations from the "Leveraging Existing Data and Analytic Methods for Health Disparities Research Related to Aging and Alzheimer's Disease and Related Dementias" Workshop Series.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
8 authors.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.