The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

Bipolar Disorder / genetics Datasets as Topic Depressive Disorder, Major / genetics Educational Status Genome-Wide Association Study Humans Intelligence / genetics Multifactorial Inheritance Psychotic Disorders / genetics Schizophrenia / genetics
bioinformatics genomics intelligence psychiatry

Journal

Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760

Informations de publication

Date de publication:
26 02 2020
Historique:
pubmed: 18 6 2019
medline: 9 2 2021
entrez: 18 6 2019
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1093/schbul/sbz061 PMID: 31206164 PMC: PMC7442352
pubmed: 31206164
pii: 5519548
doi: 10.1093/schbul/sbz061
pmc: PMC7442352
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

336-344

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800509
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH085801
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom

Informations de copyright

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

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Auteurs

Alexander L Richards (AL)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Antonio F Pardiñas (AF)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Aura Frizzati (A)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Katherine E Tansey (KE)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Amy J Lynham (AJ)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Peter Holmans (P)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Sophie E Legge (SE)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Jeanne E Savage (JE)

Complex Trait Genetics Lab, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Ingrid Agartz (I)

Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.

Ole A Andreassen (OA)

CoE NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Gabriella A M Blokland (GAM)

Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry, Harvard Medical School, Boston, MA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.

Aiden Corvin (A)

Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.

Donna Cosgrove (D)

Cognitive Genetics and Cognitive Therapy Group, Neuroimaging and Cognitive Genomics Center, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.

Franziska Degenhardt (F)

Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Institute of Human Genetics, University of Bonn, Bonn, Germany.

Srdjan Djurovic (S)

CoE NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.

Thomas Espeseth (T)

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.

Laura Ferraro (L)

Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.

Charlotte Gayer-Anderson (C)

Department of Health Service and Population Research, Institute of Psychiatry, King's College London, London, UK.

Ina Giegling (I)

Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Neeltje E van Haren (NE)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Child and Adolescent Psychiatry/Psychology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands.

Annette M Hartmann (AM)

Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

John J Hubert (JJ)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Erik G Jönsson (EG)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
CoE NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Bettina Konte (B)

Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Leonhard Lennertz (L)

Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

Loes M Olde Loohuis (LM)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA.

Ingrid Melle (I)

CoE NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Craig Morgan (C)

National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College, London, UK.

Derek W Morris (DW)

Centre for Neuroimaging and Cognitive Genomics, National University of Ireland Galway, Galway, Ireland.

Robin M Murray (RM)

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Håkan Nyman (H)

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Roel A Ophoff (RA)

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.

Jim van Os (J)

Department of Psychiatry and Medical Psychology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
Department of Psychiatry, Utrecht University Medical Centre, Utrecht, The Netherlands.
King's Health Partners Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, UK.

Tracey L Petryshen (TL)

Department of Psychiatry, Harvard Medical School, Boston, MA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.

Diego Quattrone (D)

Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Marcella Rietschel (M)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Dan Rujescu (D)

Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Bart P F Rutten (BPF)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, Maastricht, The Netherlands.

Fabian Streit (F)

Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.

Jana Strohmaier (J)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Patrick F Sullivan (PF)

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Kjetil Sundet (K)

Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Michael Wagner (M)

Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Valentina Escott-Price (V)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Michael J Owen (MJ)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Gary Donohoe (G)

Centre for Neuroimaging and Cognitive Genomics, National University of Ireland Galway, Galway, Ireland.

Michael C O'Donovan (MC)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

James T R Walters (JTR)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Troubles bipolaires et apparentés › Trouble bipolaire › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Jeux de données comme sujet › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Trouble dépressif › Trouble dépressif majeur › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Caractéristiques de la population › Facteurs socioéconomiques › Niveau d'instruction › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Personnalité › Intelligence › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Troubles psychotiques › The Relationship Between Polygenic Risk Scores...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › The Relationship Between Polygenic Risk Scores...