Genetic influences on cognitive endophenotypes in schizophrenia.
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.


CONCLUSIONS
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.
Department of Psychology, University of New Mexico, Albuquerque, NM, USA; The Mind Research Network, Albuquerque, NM, USA. Electronic address: ryeo@unm.edu.
Ronald A
RA
Yeo
Department of Psychology, University of New Mexico, Albuquerque, NM, USA.
Steven W
SW
Gangestad
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden, Germany; Dresden University of Technology, Dresden, Germany.
Esther
E
Walton
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden, Germany; Dresden University of Technology, Dresden, Germany; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Stefan
S
Ehrlich
Department of Psychology, University of New Mexico, Albuquerque, NM, USA.
Jessica
J
Pommy
The Mind Research Network, Albuquerque, NM, USA; Dept. of Psychology, Georgia State University, Atlanta, GA, USA; Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
Jessica A
JA
Turner
The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
Jingyu
J
Liu
The Mind Research Network, Albuquerque, NM, USA.
Andrew R
AR
Mayer
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
S Charles
SC
Schulz
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Beng-Choon
BC
Ho
The Mind Research Network, Albuquerque, NM, USA; Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
Juan R
JR
Bustillo
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Thomas H
TH
Wassink
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA; Minneapolis Veterans Administration Health Care System, Minneapolis, MN, USA.
Scott R
SR
Sponheim
Department of Molecular Biology, Cell Biology and Biochemistry, Laboratory for Molecular Medicine, Brown University, Providence, RI, USA.
Eric M
EM
Morrow
The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
Vince D
VD
Calhoun
D000328:Adult; D000704:Analysis of Variance; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D058068:Endophenotypes; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics*; D055815:Young Adult
Cognitive; Endophenotype; Executive function; Genetics; Mutation; Schizophrenia