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Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia
by
Smeland, Olav B.
, O’Connell, Kevin S.
, Wootton, Olivia
, Shadrin, Alexey A.
, Bjella, Thomas
, van der Meer, Dennis
, Stein, Dan J.
, Andreassen, Ole A.
, Dalvie, Shareefa
, Ueland, Torill
, Frei, Oleksandr
in
631/208/205
/ 631/208/212
/ 692/308/2056
/ Cognition - physiology
/ Cognitive ability
/ Cognitive Dysfunction - genetics
/ Female
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomics
/ Genomics - methods
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mental disorders
/ multidisciplinary
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide
/ Psychosis
/ Schizophrenia
/ Schizophrenia - genetics
/ Schizophrenic Psychology
/ Science
/ Science (multidisciplinary)
/ Statistical analysis
2024
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Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia
by
Smeland, Olav B.
, O’Connell, Kevin S.
, Wootton, Olivia
, Shadrin, Alexey A.
, Bjella, Thomas
, van der Meer, Dennis
, Stein, Dan J.
, Andreassen, Ole A.
, Dalvie, Shareefa
, Ueland, Torill
, Frei, Oleksandr
in
631/208/205
/ 631/208/212
/ 692/308/2056
/ Cognition - physiology
/ Cognitive ability
/ Cognitive Dysfunction - genetics
/ Female
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomics
/ Genomics - methods
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mental disorders
/ multidisciplinary
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide
/ Psychosis
/ Schizophrenia
/ Schizophrenia - genetics
/ Schizophrenic Psychology
/ Science
/ Science (multidisciplinary)
/ Statistical analysis
2024
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Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia
by
Smeland, Olav B.
, O’Connell, Kevin S.
, Wootton, Olivia
, Shadrin, Alexey A.
, Bjella, Thomas
, van der Meer, Dennis
, Stein, Dan J.
, Andreassen, Ole A.
, Dalvie, Shareefa
, Ueland, Torill
, Frei, Oleksandr
in
631/208/205
/ 631/208/212
/ 692/308/2056
/ Cognition - physiology
/ Cognitive ability
/ Cognitive Dysfunction - genetics
/ Female
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomics
/ Genomics - methods
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mental disorders
/ multidisciplinary
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide
/ Psychosis
/ Schizophrenia
/ Schizophrenia - genetics
/ Schizophrenic Psychology
/ Science
/ Science (multidisciplinary)
/ Statistical analysis
2024
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Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia
Journal Article
Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia
2024
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Overview
Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
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