Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/17384
Title: 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.
Authors: Sønderby, Ida E
van der Meer, Dennis
Moreau, Clara
Kaufmann, Tobias
Walters, G Bragi
Ellegaard, Maria
Abdellaoui, Abdel
Ames, David
Amunts, Katrin
Andersson, Micael
Armstrong, Nicola J
Bernard, Manon
Blackburn, Nicholas B
Blangero, John
Boomsma, Dorret I
Brodaty, Henry
Brouwer, Rachel M
Bülow, Robin
Bøen, Rune
Cahn, Wiepke
Calhoun, Vince D
Caspers, Svenja
Ching, Christopher R K
Cichon, Sven
Ciufolini, Simone
Crespo-Facorro, Benedicto
Curran, Joanne E
Dale, Anders M
Dalvie, Shareefa
Dazzan, Paola
de Geus, Eco J C
de Zubicaray, Greig I
de Zwarte, Sonja M C
Desrivieres, Sylvane
Doherty, Joanne L
Donohoe, Gary
Draganski, Bogdan
Ehrlich, Stefan
Eising, Else
Espeseth, Thomas
Fejgin, Kim
Fisher, Simon E
Fladby, Tormod
Frei, Oleksandr
Frouin, Vincent
Fukunaga, Masaki
Gareau, Thomas
Ge, Tian
Glahn, David C
Grabe, Hans J
Groenewold, Nynke A
Gústafsson, Ómar
Haavik, Jan
Haberg, Asta K
Hall, Jeremy
Hashimoto, Ryota
Hehir-Kwa, Jayne Y
Hibar, Derrek P
Hillegers, Manon H J
Hoffmann, Per
Holleran, Laurena
Holmes, Avram J
Homuth, Georg
Hottenga, Jouke-Jan
Hulshoff Pol, Hilleke E
Ikeda, Masashi
Jahanshad, Neda
Jockwitz, Christiane
Johansson, Stefan
Jönsson, Erik G
Jørgensen, Niklas R
Kikuchi, Masataka
Knowles, Emma E M
Kumar, Kuldeep
Le Hellard, Stephanie
Leu, Costin
Linden, David E J
Liu, Jingyu
Lundervold, Arvid
Lundervold, Astri Johansen
Maillard, Anne M
Martin, Nicholas G
Martin-Brevet, Sandra
Mather, Karen A
Mathias, Samuel R
McMahon, Katie L
McRae, Allan F
Medland, Sarah E
Meyer-Lindenberg, Andreas
Moberget, Torgeir
Modenato, Claudia
Sánchez, Jennifer Monereo
Morris, Derek W
Mühleisen, Thomas W
Murray, Robin M
Nielsen, Jacob
Nordvik, Jan E
Nyberg, Lars
Loohuis, Loes M Olde
Ophoff, Roel A
Owen, Michael J
Paus, Tomas
Pausova, Zdenka
Peralta, Juan M
Pike, G Bruce
Prieto, Carlos
Quinlan, Erin B
Reinbold, Céline S
Marques, Tiago Reis
Rucker, James J H
Sachdev, Perminder S
Sando, Sigrid B
Schofield, Peter R
Schork, Andrew J
Schumann, Gunter
Shin, Jean
Shumskaya, Elena
Silva, Ana I
Sisodiya, Sanjay M
Steen, Vidar M
Stein, Dan J
Strike, Lachlan T
Suzuki, Ikuo K
Tamnes, Christian K
Teumer, Alexander
Thalamuthu, Anbupalam
Tordesillas-Gutiérrez, Diana
Uhlmann, Anne
Ulfarsson, Magnus O
van 't Ent, Dennis
van den Bree, Marianne B M
Vanderhaeghen, Pierre
Vassos, Evangelos
Wen, Wei
Wittfeld, Katharina
Wright, Margaret J
Agartz, Ingrid
Djurovic, Srdjan
Westlye, Lars T
Stefansson, Hreinn
Stefansson, Kari
Jacquemont, Sébastien
Thompson, Paul M
Andreassen, Ole A
ENIGMA-CNV working group
metadata.dc.subject.mesh: Brain
Chromosome Deletion
Cognition
DNA Copy Number Variations
Female
Humans
Male
Schizophrenia
Issue Date: 22-Mar-2021
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
URI: http://hdl.handle.net/10668/17384
metadata.dc.identifier.doi: 10.1038/s41398-021-01213-0
Appears in Collections:Producción 2020

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