ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Genetic correlation analysis identifies TMEM106B, ACE, and ERC2 as genetic loci shared between Alzheimer's disease and primary psychiatric disorders.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Coordinated dysregulation of modular gene activity in human neuropathologies.bioRxiv : the preprint server for biology · 2026Article
- Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses.BMC medical genomics · 2026Article
- Longitudinal analysis of electronic health records reveals medical conditions associated with subsequent Alzheimer's disease development.Alzheimer's research & therapy · 2025Article
- Longitudinal Analysis of Electronic Health Records Reveals Medical Conditions Associated with Subsequent Alzheimer's Disease Development.medRxiv : the preprint server for health sciences · 2025Article
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15 authors.
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Abstract
introductionNeuropsychiatric symptoms (NPSs) occur in up to 85% of Alzheimer's disease (AD) cases. Current treatments - repurposed from psychiatric disorders despite limited understanding of etiologic overlap - are often ineffective.
methodsTo characterize the genetic overlap between AD and major psychiatric disorders and identify shared molecular pathways, we conducted genetic correlation analyses between AD and depression, schizophrenia, bipolar disorder, and anxiety using MiXeR and Local Analysis of [co]Variant Annotation with genome wide association studies (GWAS) summary statistics (AD: n = 487,511; bipolar disorder: n = 413,466; depression: n = 1,154,267; schizophrenia: n = 130,644; anxiety: n = 1,096,458).
resultsLocal genetic correlation analyses followed by fine mapping and functional analyses identified a missense variant in TMEM106B (rs3173615) shared between AD and depression and anxiety, a regulatory region variant in ACE (rs4292) shared between AD/schizophrenia, and two nonsense-mediated mRNA decay transcript variants in ERC2 (rs17288728; rs815460) shared between AD/anxiety. DISCUSSION: The specific molecular pathways associated with these variants provide critical information on shared etiologic components underlying these traits and inform development of improved therapeutic targets.
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