Thygesen, Johan HPresman, AmeliaHarju-Seppänen, JasmineIrizar, HaritzJones, RebeccaKuchenbaecker, KarolineLin, KuangAlizadeh, Behrooz ZAustin-Zimmerman, IsabelleBartels-Velthuis, AgnaBhat, AnjaliBruggeman, RichardCahn, WiepkeCalafato, StellaCrespo-Facorro, Benedictode Haan, Liewede-Zwarte, Sonja M CDi-Forti, MartaDiez-Revuelta, AlvaroHall, JeremyHall, Mei-HuaIyegbe, ConradJablensky, AssenKahn, ReneKalaydjieva, LubaKravariti, EugeniaLawrie, StephenLuykx, Jurjen JMata, IgancioMcDonald, ColmMcIntosh, Andrew MMcQuillin, AndrewMuir, RebeccaOphoff, RoelPicchioni, MarcoPrata, Diana PRanlund, SiriRujescu, DanRutten, Bart P FSchulze, KatjaShaikh, MadihaSchirmbeck, FrederikeSimons, Claudia J PToulopoulou, Timotheavan-Amelsvoort, Theresevan-Haren, Neeltjevan-Os, Jimvan-Winkel, RuudVassos, EvangelosWalshe, MurielWeisbrod, MatthiasZartaloudi, EiriniBell, VaughanPowell, JohnLewis, Cathryn MMurray, Robin MBramon, Elvira2023-02-092023-02-092020-07-27Thygesen JH, Presman A, Harju-Seppänen J, Irizar H, Jones R, Kuchenbaecker K, et al. Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study. Mol Psychiatry. 2021 Sep;26(9):5307-5319.http://hdl.handle.net/10668/16010The 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 .enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Predictive markersNeuroscienceGeneticsCognitionDNA Copy Number VariationsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPsychotic DisordersSchizophreniaresearch article32719466open accessEsquizofreniaRiesgoCogniciónAsociaciónEndofenotiposPacientesBiomarcadoresMetaanálisisEnfermedadGenética10.1038/s41380-020-0820-71476-5578PMC8589646https://www.nature.com/articles/s41380-020-0820-7.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589646/pdf