Browsing by Author "De Zwarte, S. M. C."

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Open Access
Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study
(Springer Nature, 2020) Thygesen, J. H.; Presman, A.; Harju-Seppanen, J.; Irizar, H.; Jones, R.; Kuchenbaecker, K.; Lin, K.; Alizadeh, B. Z.; Austin-Zimmerman, I.; Bartels-Velthuis, A.; Bhat, A.; Bruggeman, R.; Cahn, W.; Calafato, S.; Crespo-Facorro, B.; De Haan, L.; De Zwarte, S. M. C.; Di Forti, M.; Diez-Revuelta, A.; Hall, J.; Hall, M.-H.; Iyegbe, C.; Jablensky, A.; Kahn, R.; Kalaydjieva, L.; Kravariti, E.; Lawrie, S.; Luykx, J. J.; Mata, I.; McDonald, C.; McIntosh, A. M.; McQuillin, A.; Muir, R.; Ophoff, R.; Picchioni, M.; Prata, D. P.; Ranlund, S.; Rujescu, D.; Rutten, B. P. F.; Schulze, K.; Shaikh, M.; Schirmbeck, F.; Simons, C. J. P.; Toulopoulou, Timothea; Van Amelsvoort, T.; Van Haren, N.; Van Os, J.; Van Winkel, R.; Vassos, E.; Walshe, M.; Weisbrod, M.; Zartaloudi, E.; Bell, V.; Powell, J.; Lewis, C. M.; Murray, R. M.; Bramon, E.
The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.
Open Access
The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: a collaborative cognitive and neuroimaging genetics project
(Elsevier, 2018) Blokland, G. A. M.; Del Re, E. C.; Mesholam-Gately, R. I.; Jovicich, J.; Trampush, J. W.; Keshavan, M. S.; DeLisi, L. E.; Walters, J. T. R.; Turner, J. A.; Malhotra, A. K.; Lencz, T.; Shenton, M. E.; Voineskos, A. N.; Rujescu, D.; Giegling, I.; Kahn, R. S.; Roffman, J. L.; Holt, D. J.; Ehrlich, S.; Kikinis, Z.; Dazzan, P.; Murray, R. M.; Di Forti, M.; Lee, J.; Sim, K.; Lam, M.; Wolthusen, R. P. F.; De Zwarte, S. M. C.; Walton, E.; Cosgrove, D.; Kelly, S.; Maleki, N.; Osiecki, L.; Picchioni, M. M.; Bramon, E.; Russo, M.; David, A. S.; Mondelli, V.; Reinders, A. A. T. S.; Falcone, M. A.; Hartmann, A. M.; Konte, B.; Morris, D. W.; Gill, M.; Corvin, A. P.; Cahn, W.; Ho, N. F.; Liu, J. J.; Keefe, R. S. E.; Gollub, R. L.; Manoach, D. S.; Calhoun, V. D.; Schulz, S. C.; Sponheim, S. R.; Goff, D. C.; Buka, S. L.; Cherkerzian, S.; Thermenos, H. W.; Kubicki, M.; Nestor, P. G.; Dickie, E. W.; Vassos, E.; Ciufolini, S.; Marques, T. R.; Crossley, N. A.; Purcell, S. M.; Smoller, J. W.; Van Haren, N. E. M.; Toulopoulou, Timothea; Donohoe, G.; Goldstein, J. M.; Seidman, L. J.; McCarley, R. W.; Petryshen, T. L.
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 < 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 > 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.