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

Inga Margret AntonsdottirByron CreeseLambertus KleiMary Ann A DeMichele-SweetElise A WeamerPablo Garcia-GonzalezMarta MarquieMercè BoadaEmilio Alarcón-MartínSergi Valeronull nullYushi LiuBasavaraj HooliDag AarslandGeir SelbaekSverre BerghArvid RongveIngvild SaltvedtHåvard K SkjellegrindBo EngdahlOle A AndreassenBarbara BorroniPatrizia MecocciYehani WedatilakeRichard MayeuxTatiana ForoudAgustín RuizOscar L LopezM Ilyas KambohClive BallardBernie DevlinConstantine LyketsosRobert A Sweet
Published in: Alzheimer's & dementia (New York, N. Y.) (2024)
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.
Keyphrases
  • bipolar disorder
  • major depressive disorder
  • depressive symptoms
  • cognitive decline
  • genome wide
  • gene expression
  • physical activity
  • dna methylation
  • copy number