Alzheimer's & Dementia, 2024

Genetic associations with psychosis and affective disturbance in Alzheimer’s disease

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.
Genome-wide associationmeta-analysis of 9988 AD participants from six source studies with participants characterized for AD+PAD+A, and a joint phenotype (AD+A+P).
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+Awas positively correlatedwith anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereasAD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.
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.


Inga Margret Antonsdottir, Byron Creese, Lambertus Klei, Mary Ann A. DeMichele-Sweet, Elise A. Weamer, Pablo Garcia-Gonzalez, Marta Marquie, Mercè Boada, Emilio Alarcón-Martín,  Sergi Valero, NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC), AddNeuroMed Consortium, Yushi Liu, Basavaraj Hooli, Dag Aarsland, Geir Selbaek, Sverre Bergh, Arvid Rongve, Ingvild Saltvedt, Håvard K. Skjellegrind, Bo Engdahl, Ole A. Andreassen, Barbara Borroni, Patrizia Mecocci, Yehani Wedatilake, Richard Mayeux, Tatiana Foroud, Agustín Ruiz, Oscar L. Lopez, M. Ilyas Kamboh, Clive Ballard, Bernie Devlin, Constantine Lyketsos & Robert A. Sweet

Tilgang til artikkelen