title: Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.
abstract: Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population.
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA.|Department of Psychiatry, Harvard Medical School, Boston, MA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: Gabriëlla A M
authors.initials: GAM
authors.lastname: Blokland
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA.|Commonwealth Research Center, Harvard Medical School, Boston, MA.|Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Raquelle I
authors.initials: RI
authors.lastname: Mesholam-Gately
authors.affiliation: Psychology Department, Bilkent University, Ankara, Turkey.|Department of Psychology, University of Hong Kong, Pokfulam, Hong Kong.|Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA.|Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton, MA.
authors.forename: Elisabetta C
authors.initials: EC
authors.lastname: Del Re
authors.affiliation: Institute of Mental Health, Woodbridge Hospital, Singapore.
authors.forename: Max
authors.initials: M
authors.lastname: Lam
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA.|Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton, MA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: DeLisi
authors.affiliation: School of Psychology, National University of Ireland, Galway, Ireland.|Neuropsychiatric Genetics Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: James T R
authors.initials: JTR
authors.lastname: Walters
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA.|Commonwealth Research Center, Harvard Medical School, Boston, MA.|Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA.|Department of Psychiatry, Harvard Medical School, Boston, MA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Petryshen
mesh_terms: D001076:Aptitude; D003071:Cognition; D060825:Cognitive Dysfunction / Q000150:complications / Q000209:etiology / Q000235:genetics*; D058068:Endophenotypes; D056344:Executive Function; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000209:etiology / Q000235:genetics*
keywords: cognition; endophenotypes; heritability; meta-analysis; neuropsychology; twin study