ArticleAlzheimer's & dementia (New York, N. Y.)
Genetic associations with psychosis and affective disturbance in Alzheimer's disease.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Genetic susceptibility of Alzheimer's disease associated with APOE polymorphism: systematic review and bibliometric study.Journal, genetic engineering & biotechnology · 2026Review
- Recommendations for management and future investigation of psychosis in neurodegenerative disease: Findings from the International Psychogeriatric Association (IPA) working group.International psychogeriatrics · 2025Review
- GWAS links APOE to neuropsychiatric symptoms in mild cognitive impairment and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Disentangling the genetic underpinnings of neuropsychiatric symptoms in Alzheimer's disease in the Alzheimer's Disease Sequencing Project: Study design and methodology.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- Genetic associations with psychosis and affective disturbance in Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
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Abstract
introductionIndividuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.
methodsGenome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P).
resultsAD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.
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