| Title: |
Genetic associations with psychosis and affective disturbance in Alzheimer's disease |
| Authors: |
Antonsdottir, Inga Margret; Creese, Byron; Klei, Lambertus; DeMichele-Sweet, Mary Ann A.; Weamer, Elise A.; Garcia-Gonzalez, Pablo; Marquie, Marta; Boada, Mercè; Alarcón-Martín, Emilio; Valero, Sergi; NIA-LOAD Family Based Study Consortium; Alzheimer's Disease Genetics Consortium (ADGC); AddNeuroMed Consortium; Liu, Yushi; Hooli, Basavaraj; Aarsland, Dag; Selbaek, Geir; Bergh, Sverre; Rongve, Arvid; Saltvedt, Ingvild; Skjellegrind, Håvard K.; Engdahl, Bo; Andreassen, Ole A.; Borroni, Barbara; Mecocci, Patrizia; Wedatilake, Yehani; Mayeux, Richard; Foroud, Tatiana; Ruiz, Agustín; Lopez, Oscar L.; Kamboh, M. Ilyas; Ballard, Clive; Devlin, Bernie; Lyketsos, Constantine; Sweet, Robert A. |
| Contributors: |
Medical and Molecular Genetics, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Affective disturbance; Alzheimer's disease; Genome‐wide association; Heritability; Psychosis |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Alzheimer's & Dementia; Antonsdottir IM, Creese B, Klei L, et al. Genetic associations with psychosis and affective disturbance in Alzheimer's disease. Alzheimers Dement (N Y). 2024;10(2):e12472. Published 2024 May 23. doi:10.1002/trc2.12472; https://hdl.handle.net/1805/42572 |
| Availability: |
https://hdl.handle.net/1805/42572 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.72B9B5C2 |
| Database: |
BASE |