Evidence mapPaperPMID 42566636Full record

ArticleMedicine2026

Genetic evidence for a causal role of depression in late-onset Alzheimer disease: A Mendelian randomization study.

Yanlin Chen, Xiaohua Chen

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Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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2 authors.

Yanlin ChenDepartment of Neurology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, WuHan, China.ORCID 0009-0008-0538-1072
Xiaohua ChenDepartment of Neurology, Huangshi Central Hospital, Huangshi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Observational studies link psychiatric disorders to Alzheimer disease (AD), but whether these associations are causal remains unclear due to confounding and reverse causality. We aimed to dissect these relationships using genetic evidence. We performed a two-sample Mendelian randomization (MR) study to assess the causal effects of 7 psychiatric and neurodevelopmental disorders on AD and its subtypes. The primary analysis utilized the inverse-variance weighted (IVW) method, supported by comprehensive sensitivity analyses (MR Steiger test, MR-Egger, and MR-PRESSO) and a supplementary analysis excluding single nucleotide polymorphisms (SNPs) associated with potential confounders. Depression showed a significant causal association with late-onset AD (odds ratio [OR] = 1.0736, 95% confidence interval [CI]: 1.0084-1.1431, P = .0264). No significant causal associations were found for other psychiatric disorders (all P > .05). A directionality test conducted by MR Steiger confirmed our estimation of potential causal direction (P < .001). Sensitivity analyses excluding pleiotropic SNPs yielded consistent results. The causal association for depression and late-onset AD remained significant after excluding pleiotropic SNPs linked to confounders (OR = 1.0726, 95% CI: 1.0069-1.1425, P = .03). Our study provides genetic evidence supporting a causal role for depression in the etiology of late-onset AD, a link not observed for other major psychiatric disorders tested. These findings highlight the specific importance of managing depression as a potential strategy for mitigating AD risk and suggest distinct etiological pathways between different mental health conditions and neurodegeneration.

Indexed as

Alzheimer DiseaseDepressionMendelian Randomization AnalysisAge of OnsetGenetic Predisposition to DiseaseHumansPolymorphism, Single NucleotideAlzheimer diseasecausal inferenceGWASMendelian randomizationpsychiatric disorders

Identifiers

PMID42566636
PMCPMC13456805

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