Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer's Disease.

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The accumulating evidence suggests that AD involves a reconfiguration of the epigenetic landscape, including DNA methylation, post-translational modification of histone proteins, and chromatin remodeling. Along with environmental factors, individual specific genetic features play a considerable role in the formation of epigenetic architecture. In this study, we attempt to identify the non-coding regulatory SNPs (rSNPs) able to affect the epigenetic mechanisms in AD. To this end, the multi-omics approach is used. The GEO (Gene Expression Omnibus) available data (GSE153875) for AD patients and controls are integrated to reveal the rSNPs that display allele-specific features in both ChIP-seq profiles of four histone modifications and RNA-seq. Furthermore, we analyze the presence of rSNPs in the promoters of genes reported to be differentially expressed between AD and the normal brain (AD-related genes) and involved in epigenetic regulation according to the EpiFactors database. We also searched for the rSNPs in the promoters of the genes coding for transcription regulators of the identified AD-related genes. These regulators were selected based on the corresponding ChIP-seq peaks (ENCODE) in the promoter regions of these genes. Finally, we formed a panel of rSNPs localized to the promoters of genes that contribute to the epigenetic landscape in AD and, thus, to the genetic predisposition for this disease.", "claims": [{"id": "claim-method", "statement": "Two consecutive binomial tests were applied (as visualized on Figure 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37175659", "locator": "sections[12] \"4.4. Assessing Allele-Specific Events\" paragraph 2", "quote": "Two consecutive binomial tests were applied (as visualized on Figure 1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data supporting the results reported in the paper can be accessed by request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37175659", "locator": "sections[26] \"notes\" paragraph 1", "quote": "The data supporting the results reported in the paper can be accessed by request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 1563 regulatory SNPs associated with both allele-specific binding and expression within ±1000 bp of transcription start sites.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37175659", "locator": "sections[3] \"2.1. Discovering the rSNPs Associated with Allele-Specific Events\" paragraph 2", "quote": "Given the publicly available sequencing data, we have identified 1563 rSNPs associated with both allele-specific binding and expression within ±1000 bp from the TSSs (transcription start sites) or, in total, 1286 known human genes, as well as representatives for the promoter regions."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 1563 regulatory SNPs associated with both allele-specific binding and expression within ±1000 bp of transcription start sites.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37175659"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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