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The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

ABSTRACT: 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.

SUBMITTER: Richards AL

PROVIDER: S-EPMC7442352 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

Richards Alexander L AL Pardiñas Antonio F AF Frizzati Aura A Tansey Katherine E KE Lynham Amy J AJ Holmans Peter P Legge Sophie E SE Savage Jeanne E JE Agartz Ingrid I Andreassen Ole A OA Blokland Gabriella A M GAM Corvin Aiden A Cosgrove Donna D Degenhardt Franziska F Djurovic Srdjan S Espeseth Thomas T Ferraro Laura L Gayer-Anderson Charlotte C Giegling Ina I van Haren Neeltje E NE Hartmann Annette M AM Hubert John J JJ Jönsson Erik G EG Konte Bettina B Lennertz Leonhard L Olde Loohuis Loes M LM Melle Ingrid I Morgan Craig C Morris Derek W DW Murray Robin M RM Nyman Håkan H Ophoff Roel A RA van Os Jim J Petryshen Tracey L TL Quattrone Diego D Rietschel Marcella M Rujescu Dan D Rutten Bart P F BPF Streit Fabian F Strohmaier Jana J Sullivan Patrick F PF Sundet Kjetil K Wagner Michael M Escott-Price Valentina V Owen Michael J MJ Donohoe Gary G O'Donovan Michael C MC Walters James T R JTR

Schizophrenia bulletin 20200201 2

<h4>Background</h4>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.<h4>Methods</h4>We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using ...[more]

PMID: 31206164

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Project description:Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114-74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.

Dataset Information

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

Publications

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

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