TY  - JOUR
AU  - Richards, Alexander L
AU  - Pardiñas, Antonio F
AU  - Frizzati, Aura
AU  - Tansey, Katherine E
AU  - Lynham, Amy J
AU  - Holmans, Peter
AU  - Legge, Sophie E
AU  - Savage, Jeanne E
AU  - Agartz, Ingrid
AU  - Andreassen, Ole A
AU  - Blokland, Gabriella A M
AU  - Corvin, Aiden
AU  - Cosgrove, Donna
AU  - Degenhardt, Franziska
AU  - Djurovic, Srdjan
AU  - Espeseth, Thomas
AU  - Ferraro, Laura
AU  - Gayer-Anderson, Charlotte
AU  - Giegling, Ina
AU  - van Haren, Neeltje E
AU  - Hartmann, Annette M
AU  - Hubert, John J
AU  - Jönsson, Erik G
AU  - Konte, Bettina
AU  - Lennertz, Leonhard
AU  - Olde Loohuis, Loes M
AU  - Melle, Ingrid
AU  - Morgan, Craig
AU  - Morris, Derek W
AU  - Murray, Robin M
AU  - Nyman, Håkan
AU  - Ophoff, Roel A
AU  - van Os, Jim
AU  - Petryshen, Tracey L
AU  - Quattrone, Diego
AU  - Rietschel, Marcella
AU  - Rujescu, Dan
AU  - Rutten, Bart P F
AU  - Streit, Fabian
AU  - Strohmaier, Jana
AU  - Sullivan, Patrick F
AU  - Sundet, Kjetil
AU  - Wagner, Michael
AU  - Escott-Price, Valentina
AU  - Owen, Michael J
AU  - Donohoe, Gary
AU  - O’Donovan, Michael C
AU  - Walters, James T R
TI  - The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
JO  - Schizophrenia bulletin
VL  - 46
SN  - 0586-7614
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-01178
SP  - sbz061
PY  - 2019
AB  - BackgroundCognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.MethodsWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.ResultsPRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.ConclusionsCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.
KW  - Bipolar Disorder: genetics
KW  - Datasets as Topic
KW  - Depressive Disorder, Major: genetics
KW  - Educational Status
KW  - Genome-Wide Association Study
KW  - Humans
KW  - Intelligence: genetics
KW  - Multifactorial Inheritance
KW  - Psychotic Disorders: genetics
KW  - Schizophrenia: genetics
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7442352
C6  - pmid:31206164
DO  - DOI:10.1093/schbul/sbz061
UR  - https://pub.dzne.de/record/151594
ER  -