| Title: | Investigating shared risk variants and genetic etiology between Alzheimer's disease and three stress-related psychiatric disorders: a large-scale genome-wide cross-trait analysis |
| Journal: | Frontiers in Aging |
| Published: | 5 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39975850/ |
| DOI: | https://doi.org/10.3389/fragi.2025.1488528 |
Publication 14432
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Abstract
Introduction: Observational studies have reported that patients with Alzheimer's disease (AD) have a greater burden of comorbidities typically associated with stress-related psychiatric disorders. However, the contribution of hereditary factors to this comorbidity remains unclear. We evaluated phenotypic associations using observational data from the UK Biobank.</p>
Method: Our study focused on investigating the shared risk variants and genetic etiology underlying AD and three stress-related psychiatric disorders: post-traumatic stress disorder, anxiety disorder, and major depressive disorder. By leveraging summary statistics from genome-wide association studies, we investigated global genetic correlations using linkage disequilibrium score regression, genetic covariance analysis, and high-definition likelihood. Genome-wide cross-trait analysis with association analysis based on subsets and cross-phenotype association were performed to discover genome-wide significant risk variants shared between AD and the three stress-related psychiatric disorders.</p>
Results: A significant positive genetic correlation was observed between AD and major depressive disorder using linkage disequilibrium score regression (rg = 0.231; P = 0.018), genetic covariance analysis (rg = 0.138; P < 0.001), and high-definition likelihood (rg = 0.188; P < 0.001). Association analysis based on subsets and cross-phenotype association revealed thirteen risk variants in six genes shared between AD and post-traumatic stress disorder; seven risk variants in four genes shared between AD and anxiety disorder; and 23 risk variants in four genes shared between AD and major depressive disorder. Functional annotation and gene-set enrichment analysis indicated that 12 genes for comorbidity shared between patients with AD and all three stress-related psychiatric disorders were enriched in the spleen, pancreas, and whole blood.</p>
Conclusion: These results advance our knowledge of the shared genetic origins of comorbidities and pave the way for advancements in the diagnosis, management, and prevention of stress-related AD.</p>
9 Authors
- Weijia Dang
- Tianqi Hao
- Ning Li
- Hualin Zhang
- Ziqi Li
- Hongmei Yu
- Yalu Wen
- Deqiang Zheng
- Long Liu
1 Application
| Application ID | Title |
|---|---|
| 95259 | The role of dynamic environmental factors, genetic information, and gene-environment interactions in non-communicable chronic diseases and the development and validation of prediction models for risks |
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