TY - JOUR
T1 - Genetic copy number variants, cognition and psychosis
T2 - a meta-analysis and a family study
AU - Thygesen, Johan H.
AU - Presman, Amelia
AU - Harju-seppänen, Jasmine
AU - Irizar, Haritz
AU - Jones, Rebecca
AU - Kuchenbaecker, Karoline
AU - Lin, Kuang
AU - Alizadeh, Behrooz Z.
AU - Austin-zimmerman, Isabelle
AU - Bartels-velthuis, Agna
AU - Bhat, Anjali
AU - Bruggeman, Richard
AU - Cahn, Wiepke
AU - Calafato, Stella
AU - Crespo-facorro, Benedicto
AU - De Haan, Liewe
AU - De Zwarte, Sonja M. C.
AU - Di Forti, Marta
AU - Díez-revuelta, Álvaro
AU - Hall, Jeremy
AU - Hall, Mei-hua
AU - Iyegbe, Conrad
AU - Jablensky, Assen
AU - Kahn, Rene
AU - Kalaydjieva, Luba
AU - Kravariti, Eugenia
AU - Lawrie, Stephen
AU - Luykx, Jurjen J.
AU - Mata, Igancio
AU - Mcdonald, Colm
AU - Mcintosh, Andrew M.
AU - Mcquillin, Andrew
AU - Muir, Rebecca
AU - Ophoff, Roel
AU - Picchioni, Marco
AU - Prata, Diana P.
AU - Ranlund, Siri
AU - Rujescu, Dan
AU - Rutten, Bart P. F.
AU - Schulze, Katja
AU - Shaikh, Madiha
AU - Schirmbeck, Frederike
AU - Simons, Claudia J. P.
AU - Toulopoulou, Timothea
AU - Van Amelsvoort, Therese
AU - Van Haren, Neeltje
AU - Van Os, Jim
AU - Van Winkel, Ruud
AU - Vassos, Evangelos
AU - Walshe, Muriel
AU - Weisbrod, Matthias
AU - Zartaloudi, Eirini
AU - Bell, Vaughan
AU - Powell, John
AU - Lewis, Cathryn M.
AU - Murray, Robin M.
AU - Bramon, Elvira
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088661130&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-0820-7
DO - 10.1038/s41380-020-0820-7
M3 - Article
AN - SCOPUS:85088661130
SN - 1359-4184
VL - 26
SP - 5307
EP - 5319
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 9
ER -
