Genetic influences on cognitive endophenotypes in schizophrenia

Abstract Background Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. Methods The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), an...

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Published in	Schizophrenia research Vol. 156; no. 1; pp. 71 - 75
Main Authors	Yeo, Ronald A, Gangestad, Steven W, Walton, Esther, Ehrlich, Stefan, Pommy, Jessica, Turner, Jessica A, Liu, Jingyu, Mayer, Andrew R, Schulz, S. Charles, Ho, Beng-Choon, Bustillo, Juan R, Wassink, Thomas H, Sponheim, Scott R, Morrow, Eric M, Calhoun, Vince D
Format	Journal Article
Language	English
Published	Amsterdam Elsevier B.V 01.06.2014 Elsevier
Subjects	Adult Adult and adolescent clinical studies Analysis of Variance Biological and medical sciences Cognition Disorders - etiology Cognition Disorders - genetics Cognitive Endophenotype Endophenotypes Executive function Female Follow-Up Studies Genetic Association Studies Genetic Predisposition to Disease - genetics Genetics Humans Male Medical sciences Mutation Neuropsychological Tests Principal Component Analysis Psychiatric Status Rating Scales Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Schizophrenia Schizophrenia - complications Schizophrenia - genetics Young Adult Schizophrenia Genetics Executive function Cognitive Mutation Endophenotype Psychosis Human Cognition Genetic determinism
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Abstract	Abstract Background Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. Methods The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). Results Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. Limitations Though adequately powered, our sample size is small for a genetic study. Conclusions These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.
AbstractList	BACKGROUNDCognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. METHODSThe current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). RESULTSCognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. LIMITATIONSThough adequately powered, our sample size is small for a genetic study. CONCLUSIONSThese results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls. Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. Though adequately powered, our sample size is small for a genetic study. These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls. Abstract Background Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. Methods The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). Results Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. Limitations Though adequately powered, our sample size is small for a genetic study. Conclusions These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.
Author	Mayer, Andrew R Morrow, Eric M Sponheim, Scott R Liu, Jingyu Gangestad, Steven W Yeo, Ronald A Ehrlich, Stefan Pommy, Jessica Walton, Esther Schulz, S. Charles Wassink, Thomas H Bustillo, Juan R Turner, Jessica A Calhoun, Vince D Ho, Beng-Choon
AuthorAffiliation	10 Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA 12 Department of Molecular Biology, Cell Biology and Biochemistry, Laboratory for Molecular Medicine, Brown University, Providence, RI, USA 6 Dept of Psychology and the Neuroscience Institute, Georgia State University, Atlanta, GA 8 Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA 7 Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA 3 MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA 5 Department of Psychiatry, Massachusetts General Hospital, Boston, MA 11 Minneapolis Veterans Administration Health Care System, Minneapolis, MN, USA 1 Department of Psychology, University of New Mexico, Albuquerque, NM, USA 2 The Mind Research Network, Albuquerque, NM, USA 4 Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany 9 Depart
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CitedBy_id	crossref_primary_10_1016_j_psychres_2016_12_027 crossref_primary_10_1155_2018_2686045 crossref_primary_10_1016_j_jtcc_2018_02_002 crossref_primary_10_1016_j_psychres_2015_04_045 crossref_primary_10_1016_j_schres_2017_09_024 crossref_primary_10_1016_j_scog_2018_01_001 crossref_primary_10_1016_j_neubiorev_2015_04_022 crossref_primary_10_1093_schbul_sbw146 crossref_primary_10_1017_S1355617715000867 crossref_primary_10_1016_j_pharep_2017_11_013 crossref_primary_10_1017_S0033291715001701 crossref_primary_10_1016_j_euroneuro_2014_12_006
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Snippet	Abstract Background Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. Methods The current study... Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. The current study investigated the importance of... BACKGROUNDCognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. METHODSThe current study investigated...
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SubjectTerms	Adult Adult and adolescent clinical studies Analysis of Variance Biological and medical sciences Cognition Disorders - etiology Cognition Disorders - genetics Cognitive Endophenotype Endophenotypes Executive function Female Follow-Up Studies Genetic Association Studies Genetic Predisposition to Disease - genetics Genetics Humans Male Medical sciences Mutation Neuropsychological Tests Principal Component Analysis Psychiatric Status Rating Scales Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Schizophrenia Schizophrenia - complications Schizophrenia - genetics Young Adult
Title	Genetic influences on cognitive endophenotypes in schizophrenia
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