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@ARTICLE{Committee:867608,
author = {Committee, Writing and van der Meer, Dennis and Sønderby,
Ida E and Kaufmann, Tobias and Walters, G Bragi and
Abdellaoui, Abdel and Ames, David and Amunts, Katrin and
Andersson, Micael and Armstrong, Nicola J and Bernard, Manon
and Blackburn, Nicholas B and Blangero, John and Boomsma,
Dorret I and Brodaty, Henry and Brouwer, Rachel M and
Bülow, Robin and Cahn, Wiepke and Calhoun, Vince D and
Caspers, Svenja and Cavalleri, Gianpiero L and Ching,
Christopher R K and Cichon, Sven and Ciufolini, Simone and
Corvin, Aiden and Crespo-Facorro, Benedicto and Curran,
Joanne E and Dalvie, Shareefa and Dazzan, Paola and de Geus,
Eco J C and de Zubicaray, Greig I and de Zwarte, Sonja M C
and Delanty, Norman and den Braber, Anouk and Desrivieres,
Sylvane and Di Forti, Marta and Doherty, Joanne L and
Donohoe, Gary and Ehrlich, Stefan and Eising, Else and
Espeseth, Thomas and Fisher, Simon E and Fladby, Tormod and
Frei, Oleksandr and Frouin, Vincent and Fukunaga, Masaki and
Gareau, Thomas and Glahn, David C and Grabe, Hans J and
Groenewold, Nynke A and Gústafsson, Ómar and Haavik, Jan
and Haberg, Asta K and Hashimoto, Ryota and Hehir-Kwa, Jayne
Y and Hibar, Derrek P and Hillegers, Manon H J and Hoffmann,
Per and Holleran, Laurena and Hottenga, Jouke-Jan and
Hulshoff Pol, Hilleke E and Ikeda, Masashi and Jacquemont,
Sébastien and Jahanshad, Neda and Jockwitz, Christiane and
Johansson, Stefan and Jönsson, Erik G and Kikuchi, Masataka
and Knowles, Emma E M and Kwok, John B and Le Hellard,
Stephanie and Linden, David E J and Liu, Jingyu and
Lundervold, Arvid and Lundervold, Astri J and Martin,
Nicholas G and Mather, Karen A and Mathias, Samuel R and
McMahon, Katie L and McRae, Allan F and Medland, Sarah E and
Moberget, Torgeir and Moreau, Clara and Morris, Derek W and
Mühleisen, Thomas W and Murray, Robin M and Nordvik, Jan E
and Nyberg, Lars and Olde Loohuis, Loes M and Ophoff, Roel A
and Owen, Michael J and Paus, Tomas and Pausova, Zdenka and
Peralta, Juan M and Pike, Bruce and Prieto, Carlos and
Quinlan, Erin Burke and Reinbold, Céline S and Reis
Marques, Tiago and Rucker, James J H and Sachdev, Perminder
S and Sando, Sigrid B and Schofield, Peter R and Schork,
Andrew J and Schumann, Gunter and Shin, Jean and Shumskaya,
Elena and Silva, Ana I and Sisodiya, Sanjay M and Steen,
Vidar M and Stein, Dan J and Strike, Lachlan T and Tamnes,
Christian K and Teumer, Alexander and Thalamuthu, Anbupalam
and Tordesillas-Gutiérrez, Diana and Uhlmann, Anne and
Úlfarsson, Magnús Ö and van 't Ent, Dennis and van den
Bree, Marianne B M and Vassos, Evangelos and Wen, Wei and
Wittfeld, Katharina and Wright, Margaret J and Zayats,
Tetyana and Dale, Anders M and Djurovic, Srdjan and Agartz,
Ingrid and Westlye, Lars T and Stefánsson, Hreinn and
Stefánsson, Kári and Thompson, Paul M and Andreassen, Ole
A},
collaboration = {Group, ENIGMA-CNV Working},
title = {{A}ssociation of {C}opy {N}umber {V}ariation of the 15q11.2
{BP}1-{BP}2 {R}egion {W}ith {C}ortical and {S}ubcortical
{M}orphology and {C}ognition.},
journal = {JAMA psychiatry},
volume = {77},
number = {4},
issn = {2168-622X},
address = {Chicago, Ill.},
publisher = {AMA},
reportid = {FZJ-2019-06229},
pages = {420-430},
year = {2020},
abstract = {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.},
cin = {INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {571 - Connectivity and Activity (POF3-571)},
pid = {G:(DE-HGF)POF3-571},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31665216},
pmc = {pmc:PMC6822096},
UT = {WOS:000525168200014},
doi = {10.1001/jamapsychiatry.2019.3779},
url = {https://juser.fz-juelich.de/record/867608},
}