Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer disease: meta-analysis of 11 cohort studies

Byron Creese; Evangelos Vassos; Sverre Bergh; Lavinia Athanasiu; Iskandar Johar; Arvid Rongve; Ingrid Tøndel Medbøen; Miguel Vasconcelos Da Silva; Eivind Aakhus; Fred Andersen; Francesco Bettella; Anne Brækhus; Srdjan Djurovic; Giulia Paroni; Petroula Proitsi; Ingvild Tina Saltvedt; Davide Seripa; Eystein Stordal; Tormod Fladby; Dag Aarsland; Ole A. Andreassen; Clive G. Ballard; Geir Selbæk

doi:10.1038/s41398-019-0592-5

GenomicsTranslational PsychiatryOct 22, 2019

Peer-reviewed journal article

Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer disease: meta-analysis of 11 cohort studies

Byron Creese iD, Evangelos Vassos iD, Sverre Bergh iD, Lavinia Athanasiu iD, Iskandar Johar, Arvid Rongve iD, Ingrid Tøndel Medbøen iD, Miguel Vasconcelos Da Silva iD, Eivind Aakhus iD, Fred Andersen, Francesco Bettella iD, Anne Brækhus, Srdjan Djurovic iD, Giulia Paroni iD, Petroula Proitsi iD, Ingvild Tina Saltvedt iD, Davide Seripa iD, Eystein Stordal iD, Tormod Fladby iD, Dag Aarsland iD, Ole A. Andreassen iD, Clive G. Ballard iD, Geir Selbæk iD

Abstract

BackgroundPsychosis (delusions and hallucinations) is common in Alzheimers disease (AD) and associated with worse clinical outcomes including accelerated cognitive decline and shorter time to nursing home admission. Atypical antipsychotics have limited efficacy which, along with emerging genomic research, suggests some overlapping mechanisms with other disorders characterized by psychosis, like schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with psychotic symptoms in AD. MethodsSchizophrenia PRS was calculated using Psychiatric Genomics Consortium data at 10 GWAS p-value thresholds (PT) in 3,173 AD cases from 11 cohort studies. Association between PRS and AD psychosis status was tested by logistic regression in each cohort individually and the results meta-analyzed. ResultsThe schizophrenia PRS was associated with psychosis in AD at an optimum PT of The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.17-fold increased risk (95% CI: 1.07-1.3; p=0.001). ConclusionThese new findings point towards psychosis in AD - and particularly delusions - sharing some genetic liability with schizophrenia, and support a transdiagnostic view of psychotic symptoms across the lifespan.

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