TY - JOUR

T1 - The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

AU - GROUP Investigators

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

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

AU - Knight, Jo

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - BACKGROUND: Cognitive 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.METHODS: We 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.RESULTS: PRS 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.CONCLUSIONS: Cognition 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.

AB - BACKGROUND: Cognitive 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.METHODS: We 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.RESULTS: PRS 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.CONCLUSIONS: Cognition 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.

U2 - 10.1093/schbul/sbz061

DO - 10.1093/schbul/sbz061

M3 - Journal article

C2 - 31206164

VL - 46

SP - 336

EP - 344

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 2

ER -