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Heritability of neuropsychological measures in Schizophrenia and non-psychiatric populations: a systematic review and meta-analysis

Blokland, Gabriëlla A. M., Mesholam-Gately, Raquelle I., Toulopoulou, Timothea, del Re, Elisabetta C., Lam, Max, DeLisi, Lynn E., Donohoe, Gary, Walters, James, Seidman, Larry J. and Petryshen, Tracey L. 2017. Heritability of neuropsychological measures in Schizophrenia and non-psychiatric populations: a systematic review and meta-analysis. Schizophrenia Bulletin 43 (4) , pp. 788-800. 10.1093/schbul/sbw146

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Oxford University Press
ISSN: 0586-7614
Date of First Compliant Deposit: 19 March 2018
Date of Acceptance: 22 September 2016
Last Modified: 26 Apr 2018 05:13
URI: http://orca-mwe.cf.ac.uk/id/eprint/109986

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