Common genetic risk variants are associated with positive symptoms and decision-making ability in patients with schizophrenia

Martin, Andrew K.; Robinson, Gail; Reutens, David C.; Mowry, Bryan

doi:10.1016/j.psychres.2015.04.045

Cited by 6 publications

(5 citation statements)

References 18 publications

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“…Unfortunately, the few patient studies examining schizophrenia genetic variants in cognition produced inconsistent results, possibly due to small sample sizes. [84][85][86] In addition, there have been no studies specifically examining the genetic basis of the degree of cognitive impairment in patients separate from the genetic basis of cognitive ability. While schizophrenia risk genes may influence the degree of impairment, as suggested by the presence of cognitive deficits in unaffected relatives genetically predisposed to schizophrenia, 9,[64][65][66][67] other genes that are not causal in schizophrenia may be involved.…”

Section: Heritability Of Neuropsychological Measuresmentioning

confidence: 99%

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis

Blokland

Mesholam-Gately

Toulopoulou

et al. 2016

Schizophrenia Bulletin

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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.

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Section: Heritability Of Neuropsychological Measuresmentioning

confidence: 99%

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis

Blokland

Mesholam-Gately

Toulopoulou

et al. 2016

Schizophrenia Bulletin

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“…Moderate to high genetic correlations between schizophrenia and cognitive and brain structural phenotypes (r g = 0.5–0.8) suggest a partially shared genetic etiology (Blokland et al, 2016; Bohlken et al, 2016; Lee et al, 2016). Indeed, polygenic risk for schizophrenia is significantly associated with prefrontal inefficiency during working memory performance in patients and controls (Walton et al, 2013a; Walton et al, 2013b), as well as lower cognitive performance among healthy populations (Germine et al, 2016; Hubbard et al, 2016; Lencz et al, 2014; Liebers et al, 2016) and schizophrenia patients (Martin et al, 2015). Specific genetic risk variants have also been associated with altered cognition and brain structure among patients (Donohoe et al, 2010; 2013; Lencz et al, 2010; Martin et al, 2015; Wassink et al, 2012; Yeo et al, 2014) although some studies are negative (van Scheltinga et al, 2013), possibly due to the use of small samples that are prone to inconsistent results.…”

Section: Introductionmentioning

confidence: 99%

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

Blokland

Mesholam-Gately

et al. 2018

Schizophrenia Research

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Background: Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. Methods: We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/ or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site.Results: Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p b 1 × 10 −10). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. Conclusions: The Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of N 10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia.

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“…This threshold was identified to have the greatest predictive power when using a meta-analysis of previous GWAS as the target sample and the Molecular Genetics of Schizophrenia (MGS) dataset as the discovery sample (Schizophrenia Working Group of the Psychiatric Genomics, 2014). In addition to common variants, rare structural variants have also been associated with schizophrenia risk (Mowry & Gratten, 2013) as well as clinical and cognitive phenotypic differences in patients with schizophrenia (Martin et al 2014 a , 2015 b ). Aggregate measures of copy number variant (CNV) burden have been associated with differences in clinical (Yeo et al 2013; Martin et al 2015 a ), cognitive (Yeo et al 2013, 2014; Martin et al 2014 c ), and neuroimaging domains (Martin et al 2014 b , c ) and are potentially of interest in genetic studies of treatment resistance.…”

Section: Introductionmentioning

confidence: 99%

Increased rare duplication burden genomewide in patients with treatment-resistant schizophrenia

Martin

Mowry

2015

Psychol. Med.

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Common genetic risk variants are associated with positive symptoms and decision-making ability in patients with schizophrenia

Cited by 6 publications

References 18 publications

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

Increased rare duplication burden genomewide in patients with treatment-resistant schizophrenia

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