Genetic associations with psychosis and affective disturbance in Alzheimer's disease
Antonsdottir, Inga Margaret; Creese, Byron; Klei, Lambertus; DeMichele-Sweet, Mary Ann A.; Weamer, Elise A.; Garcia-Gonzalez, Pablo; Marquié, Marta; Boada, Mercé; Alarcón-Martín, Emilio; Valero, Sergi; Liu, Yushi; Hooli, Basavaraj; Aarsland, Dag; Selbæk, Geir; Bergh, Sverre; Rongve, Arvid; Saltvedt, Ingvild Tina; Skjellegrind, Håvard Kjesbu; Engdahl, Bo Lars; Andreassen, Ole; Borroni, Barbara; Mecocci, Patrizia; Wedatilake, Yehani; Mayeux, Richard; Foroud, Tatiana M.; Ruiz, Agustin; Lopez, Oscar L.; Kamboh, M. Ilyas; Ballard, Clive; Devlin, Bernie; Lyketsos, Constantine; Sweet, Robert A.
Peer reviewed, Journal article
Published version
![Thumbnail](/uis-xmlui/bitstream/handle/11250/3149385/Genetic%2bassociations%2bwith%2bpsychosis%2band%2baffective%2bdisturbance_Bergh%252BWedatilake_2024.pdf.jpg?sequence=6&isAllowed=y)
Date
2024Metadata
Show full item recordCollections
Original version
Antonsdottir, I. M., Creese, B., Klei, L., DeMichele‐Sweet, M. A. A., Weamer, E. A., Garcia‐Gonzalez, P., ... & Sweet, R. A. (2024). Genetic associations with psychosis and affective disturbance in Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 10(2), e12472. 10.1002/trc2.12472Abstract
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.