TY - JOUR
T1 - 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
AU - Sønderby, Ida E.
AU - van der Meer, Dennis
AU - Moreau, Clara
AU - Kaufmann, Tobias
AU - Walters, G. Bragi
AU - Ellegaard, Maria
AU - Abdellaoui, Abdel
AU - Ames, David
AU - Amunts, Katrin
AU - Andersson, Micael
AU - Armstrong, Nicola J.
AU - Bernard, Manon
AU - Blackburn, Nicholas B.
AU - Blangero, John
AU - Boomsma, Dorret I.
AU - Brodaty, Henry
AU - Brouwer, Rachel M.
AU - Bülow, Robin
AU - Bøen, Rune
AU - Cahn, Wiepke
AU - Calhoun, Vince D.
AU - Caspers, Svenja
AU - Ching, Christopher R.K.
AU - Cichon, Sven
AU - Ciufolini, Simone
AU - Crespo-Facorro, Benedicto
AU - Curran, Joanne E.
AU - Dale, Anders M.
AU - Dalvie, Shareefa
AU - Dazzan, Paola
AU - de Geus, Eco J.C.
AU - de Zubicaray, Greig I.
AU - de Zwarte, Sonja M.C.
AU - Desrivieres, Sylvane
AU - Doherty, Joanne L.
AU - Donohoe, Gary
AU - Draganski, Bogdan
AU - Ehrlich, Stefan
AU - Eising, Else
AU - Espeseth, Thomas
AU - Fejgin, Kim
AU - Fisher, Simon E.
AU - Fladby, Tormod
AU - Frei, Oleksandr
AU - Frouin, Vincent
AU - Fukunaga, Masaki
AU - Gareau, Thomas
AU - Ge, Tian
AU - Glahn, David C.
AU - Grabe, Hans J.
AU - Groenewold, Nynke A.
AU - Gústafsson, Ómar
AU - Haavik, Jan
AU - Haberg, Asta K.
AU - Hall, Jeremy
AU - Hashimoto, Ryota
AU - Hehir-Kwa, Jayne Y.
AU - Hibar, Derrek P.
AU - Hillegers, Manon H.J.
AU - Hoffmann, Per
AU - Holleran, Laurena
AU - Holmes, Avram J.
AU - Homuth, Georg
AU - Hottenga, Jouke Jan
AU - Hulshoff Pol, Hilleke E.
AU - Ikeda, Masashi
AU - Jahanshad, Neda
AU - Jockwitz, Christiane
AU - Johansson, Stefan
AU - Jönsson, Erik G.
AU - Jørgensen, Niklas R.
AU - Kikuchi, Masataka
AU - Knowles, Emma E.M.
AU - Kumar, Kuldeep
AU - Le Hellard, Stephanie
AU - Leu, Costin
AU - Linden, David E.J.
AU - Liu, Jingyu
AU - Lundervold, Arvid
AU - Lundervold, Astri Johansen
AU - Maillard, Anne M.
AU - Martin, Nicholas G.
AU - Martin-Brevet, Sandra
AU - Mather, Karen A.
AU - Mathias, Samuel R.
AU - McMahon, Katie L.
AU - McRae, Allan F.
AU - Medland, Sarah E.
AU - Meyer-Lindenberg, Andreas
AU - Moberget, Torgeir
AU - Modenato, Claudia
AU - Sánchez, Jennifer Monereo
AU - Morris, Derek W.
AU - Mühleisen, Thomas W.
AU - Murray, Robin M.
AU - Nielsen, Jacob
AU - Nordvik, Jan E.
AU - Nyberg, Lars
AU - Loohuis, Loes M.Olde
AU - Ophoff, Roel A.
AU - Owen, Michael J.
AU - Paus, Tomas
AU - Pausova, Zdenka
AU - Peralta, Juan M.
AU - Pike, G. Bruce
AU - Prieto, Carlos
AU - Quinlan, Erin B.
AU - Reinbold, Céline S.
AU - Marques, Tiago Reis
AU - Rucker, James J.H.
AU - Sachdev, Perminder S.
AU - Sando, Sigrid B.
AU - Schofield, Peter R.
AU - Schork, Andrew J.
AU - Schumann, Gunter
AU - Shin, Jean
AU - Shumskaya, Elena
AU - Silva, Ana I.
AU - Sisodiya, Sanjay M.
AU - Steen, Vidar M.
AU - Stein, Dan J.
AU - Strike, Lachlan T.
AU - Suzuki, Ikuo K.
AU - Tamnes, Christian K.
AU - Teumer, Alexander
AU - Thalamuthu, Anbupalam
AU - Tordesillas-Gutiérrez, Diana
AU - Uhlmann, Anne
AU - Ulfarsson, Magnus O.
AU - van 't Ent, Dennis
AU - van den Bree, Marianne B.M.
AU - Vanderhaeghen, Pierre
AU - Vassos, Evangelos
AU - Wen, Wei
AU - Wittfeld, Katharina
AU - Wright, Margaret J.
AU - Agartz, Ingrid
AU - Djurovic, Srdjan
AU - Westlye, Lars T.
AU - Stefansson, Hreinn
AU - Stefansson, Kari
AU - Jacquemont, Sébastien
AU - Thompson, Paul M.
AU - Andreassen, Ole A.
AU - ENIGMA-CNV working group
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/3/22
Y1 - 2021/3/22
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-021-01213-0
DO - 10.1038/s41398-021-01213-0
M3 - Article
C2 - 33753722
SN - 2158-3188
VL - 11
SP - 182
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 182
ER -