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http://bura.brunel.ac.uk/handle/2438/29551| Title: | Genetic associations with psychosis and affective disturbance in Alzheimer's disease |
| Authors: | Antonsdottir, IM Creese, B Klei, L DeMichele-Sweet, MAA Weamer, EA Garcia-Gonzalez, P Marquie, M Boada, M Alarcón-Martín, E Valero, S NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC) AddNeuroMed Consortium Liu, Y Hooli, B Aarsland, D Selbaek, G Bergh, S Rongve, A Saltvedt, I Skjellegrind, HK Engdahl, B Andreassen, OA Borroni, B Mecocci, P Wedatilake, Y Mayeux, R Foroud, T Ruiz, A Lopez, OL Kamboh, MI Ballard, C Devlin, B Lyketsos, C Sweet, RA |
| Keywords: | affective disturbance;Alzheimer's disease;genome-wide association;heritability;psychosis |
| Issue Date: | 23-May-2024 |
| Publisher: | Wiley on behalf of Alzheimer's Association |
| Citation: | Antonsdottir, I.M. et al. (2024) 'Genetic associations with psychosis and affective disturbance in Alzheimer's disease', Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 10 (2), e12472, pp. 1 - 11. doi: 10.1002/trc2.12472. |
| Abstract: | INTRODUCTION: Individuals 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. METHODS: Genome-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). RESULTS: AD+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. |
| Description: | Inga Margret Antonsdottir, Constantine Lyketsos, and Robert A. Sweet contributed equally to this study. 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. |
| URI: | https://bura.brunel.ac.uk/handle/2438/29551 |
| DOI: | https://doi.org/10.1002/trc2.12472 |
| ISSN: | 2352-8737 |
| Other Identifiers: | ORCiD: Byron Creese https://orcid.org/0000-0001-6490-6037 e12472 |
| Appears in Collections: | Dept of Life Sciences Research Papers |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| FullText.pdf | Copyright © 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | 1.15 MB | Adobe PDF | View/Open |
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