Genetic associations with psychosis and affective disturbance in Alzheimer's disease.

Autor: Antonsdottir IM; Johns Hopkins School of Nursing Baltimore Maryland USA.; Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Department of Psychiatry and Behavioral Sciences Johns Hopkins Bayview Johns Hopkins Medicine Baltimore Maryland USA., Creese B; Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter Exeter UK., Klei L; Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA., DeMichele-Sweet MAA; Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA., Weamer EA; Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA., Garcia-Gonzalez P; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos III Madrid Spain., Marquie M; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos III Madrid Spain., Boada M; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos III Madrid Spain., Alarcón-Martín E; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain., Valero S; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos III Madrid Spain., Liu Y; Global Statistical Science Lilly Research Laboratories Eli Lilly and Company Indianapolis Indiana USA., Hooli B; Neurodegeneration Research Lilly Research Laboratories Eli Lilly and Company Indianapolis Indiana USA., Aarsland D; Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London England., Selbaek G; Norwegian National Centre for Aging and Health Vestfold Hospital Trust Tønsberg Norway.; Department Geriatric Medicine Oslo University Hospital Oslo Norway., Bergh S; Research Centre of Age-related Functional Decline and Disease Innlandet Hospital Trust Ottestad Norway., Rongve A; Department of Research and Innovation Helse Fonna Haugesund Norway.; Department of Clinical Medicine (K1) University of Bergen Bergen Norway., Saltvedt I; Geriatric Department St. Olav Hospital University Hospital of Trondheim Trondheim Norway., Skjellegrind HK; Nord-Trøndelag Hospital Trust Levanger Norway.; HUNT Research Centre Department of Public Health and Nursing Faculty of Medicine and Health Sciences Norwegian University of Science and Technology Levanger Norway., Engdahl B; Norwegian Institute of Public Health Oslo Norway., Andreassen OA; NORMENT, Institute of Clinical Medicine University of Oslo Oslo Norway., Borroni B; Centre for Neurodegenerative Disorders University of Brescia Brescia Italy., Mecocci P; Institute of Gerontology and Geriatrics University of Perugia Perugia Italy.; Geriatric Clinic NVS Karolinska Institutet Stockholm Sweden., Wedatilake Y; Research Centre of Age-related Functional Decline and Disease Innlandet Hospital Trust Ottestad Norway., Mayeux R; Departments of Neurology Psychiatry and Epidemiology Columbia University New York New York USA., Foroud T; Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA., Ruiz A; Research Center and Memory Clinic ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos III Madrid Spain., Lopez OL; Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA.; Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA., Kamboh MI; Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA., Ballard C; Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter Exeter UK., Devlin B; Department of Human Genetics University of Pittsburgh Pittsburgh Pennsylvania USA., Lyketsos C; Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Department of Psychiatry and Behavioral Sciences Johns Hopkins Bayview Johns Hopkins Medicine Baltimore Maryland USA., Sweet RA; Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA.; Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (New York, N. Y.) [Alzheimers Dement (N Y)] 2024 May 23; Vol. 10 (2), pp. e12472. Date of Electronic Publication: 2024 May 23 (Print Publication: 2024).
DOI: 10.1002/trc2.12472
Abstrakt: 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.
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.
Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information.
(© 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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