TY - JOUR
T1 - The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
AU - Richards, Alexander L.
AU - Pardinas, 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 - Jonsson, Erik G.
AU - Konte, Bettina
AU - Lennertz, Leonhard
AU - Loohuis, Loes M. Olde
AU - Melle, Ingrid
AU - Morgan, Craig
AU - Morris, Derek W.
AU - Murray, Robin M.
AU - Nyman, Hakan
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 - GRP Investigators
AU - EUGEI WP2 Group
AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium
N1 - Funding Information:
K. G. Jebsen Stiftelsen. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health and Social Care. PF Sullivan reports the following potentially competing financial interests. Current: Lundbeck (advisory committee, grant recipient). Past 3 years: Pfizer (scientific advisory board), Element Genomics (consultation fee), and Roche (speaker reimbursement). CM Bulik (spouse) reports: Shire (grant recipient, Scientific Advisory Board member); Pearson and Walker (author, royalty recipient); OpenBiome (collaborator); uBiome (grant recipient/ collaborator); Recovery Record (collaborator). These interests are unrelated to this project. M.J.O., M.C.O., J.T.R.W. are supported by a collaborative research grant from Takeda. Takeda played no part in the conception, design, implementation, or interpretation of this study, which was completed before the funding award. No other conflicts of interest are reported.
Funding Information:
Cardiff University researchers were supported by Medical Research Council (MRC) Centre (G0800509) and Programme Grant (G0801418). This study was supported by the NIMH PGC grant (5U01MH109514-02). The EU-GEI Project was funded by the European Community’s Seventh Framework Programme under grant agreement HEALTH-F2-2010–241909 (Project EU-GEI). This article represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London.
Publisher Copyright:
© The Author(s) 2019.
PY - 2020/3
Y1 - 2020/3
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 x 10(-28)) and EA (P = 1.27 x 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 x 10(-28)) and EA (P = 1.27 x 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.
KW - psychiatry
KW - genomics
KW - intelligence
KW - bioinformatics
KW - GENOME-WIDE ASSOCIATION
KW - COMMON VARIANTS
KW - INTELLIGENCE
KW - ABILITY
KW - MEMORY
KW - ENDOPHENOTYPES
KW - HERITABILITY
KW - METAANALYSIS
KW - PERFORMANCE
KW - CONSORTIUM
U2 - 10.1093/schbul/sbz061
DO - 10.1093/schbul/sbz061
M3 - Article
C2 - 31206164
SN - 0586-7614
VL - 46
SP - 336
EP - 344
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 2
ER -