RT Journal Article
T1 Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.
A1 Writing Committee for the ENIGMA-CNV Working Group, 
A1 van der Meer, Dennis
A1 Sønderby, Ida E
A1 Kaufmann, Tobias
A1 Walters, G Bragi
A1 Abdellaoui, Abdel
A1 Ames, David
A1 Amunts, Katrin
A1 Andersson, Micael
A1 Armstrong, Nicola J
A1 Bernard, Manon
A1 Blackburn, Nicholas B
A1 Blangero, John
A1 Boomsma, Dorret I
A1 Brodaty, Henry
A1 Brouwer, Rachel M
A1 Bülow, Robin
A1 Cahn, Wiepke
A1 Calhoun, Vince D
A1 Caspers, Svenja
A1 Cavalleri, Gianpiero L
A1 Ching, Christopher R K
A1 Cichon, Sven
A1 Ciufolini, Simone
A1 Corvin, Aiden
A1 Crespo-Facorro, Benedicto
A1 Curran, Joanne E
A1 Dalvie, Shareefa
A1 Dazzan, Paola
A1 de Geus, Eco J C
A1 de Zubicaray, Greig I
A1 de Zwarte, Sonja M C
A1 Delanty, Norman
A1 den Braber, Anouk
A1 Desrivieres, Sylvane
A1 Di Forti, Marta
A1 Doherty, Joanne L
A1 Donohoe, Gary
A1 Ehrlich, Stefan
A1 Eising, Else
A1 Espeseth, Thomas
A1 Fisher, Simon E
A1 Fladby, Tormod
A1 Frei, Oleksandr
A1 Frouin, Vincent
A1 Fukunaga, Masaki
A1 Gareau, Thomas
A1 Glahn, David C
A1 Grabe, Hans J
A1 Groenewold, Nynke A
A1 Gústafsson, Ómar
A1 Haavik, Jan
A1 Haberg, Asta K
A1 Hashimoto, Ryota
A1 Hehir-Kwa, Jayne Y
A1 Hibar, Derrek P
A1 Hillegers, Manon H J
A1 Hoffmann, Per
A1 Holleran, Laurena
A1 Hottenga, Jouke-Jan
A1 Hulshoff Pol, Hilleke E
A1 Ikeda, Masashi
A1 Jacquemont, Sébastien
A1 Jahanshad, Neda
A1 Jockwitz, Christiane
A1 Johansson, Stefan
A1 Jönsson, Erik G
A1 Kikuchi, Masataka
A1 Knowles, Emma E M
A1 Kwok, John B
A1 Le Hellard, Stephanie
A1 Linden, David E J
A1 Liu, Jingyu
A1 Lundervold, Arvid
A1 Lundervold, Astri J
A1 Martin, Nicholas G
A1 Mather, Karen A
A1 Mathias, Samuel R
A1 McMahon, Katie L
A1 McRae, Allan F
A1 Medland, Sarah E
A1 Moberget, Torgeir
A1 Moreau, Clara
A1 Morris, Derek W
A1 Mühleisen, Thomas W
A1 Murray, Robin M
A1 Nordvik, Jan E
A1 Nyberg, Lars
A1 Olde Loohuis, Loes M
A1 Ophoff, Roel A
A1 Owen, Michael J
A1 Paus, Tomas
A1 Pausova, Zdenka
A1 Peralta, Juan M
A1 Pike, Bruce
A1 Prieto, Carlos
A1 Quinlan, Erin Burke
A1 Reinbold, Céline S
A1 Reis Marques, Tiago
A1 Rucker, James J H
A1 Sachdev, Perminder S
A1 Sando, Sigrid B
A1 Schofield, Peter R
A1 Schork, Andrew J
A1 Schumann, Gunter
A1 Shin, Jean
A1 Shumskaya, Elena
A1 Silva, Ana I
A1 Sisodiya, Sanjay M
A1 Steen, Vidar M
A1 Stein, Dan J
A1 Strike, Lachlan T
A1 Tamnes, Christian K
A1 Teumer, Alexander
A1 Thalamuthu, Anbupalam
A1 Tordesillas-Gutiérrez, Diana
A1 Uhlmann, Anne
A1 Úlfarsson, Magnús Ö
A1 van 't Ent, Dennis
A1 van den Bree, Marianne B M
A1 Vassos, Evangelos
A1 Wen, Wei
A1 Wittfeld, Katharina
A1 Wright, Margaret J
A1 Zayats, Tetyana
A1 Dale, Anders M
A1 Djurovic, Srdjan
A1 Agartz, Ingrid
A1 Westlye, Lars T
A1 Stefánsson, Hreinn
A1 Stefánsson, Kári
A1 Thompson, Paul M
A1 Andreassen, Ole A
AB Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks. These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
YR 2020
FD 2020
LK https://hdl.handle.net/10668/24443
UL https://hdl.handle.net/10668/24443
LA en
DS RISalud
RD Apr 11, 2025