Sønderby, Ida Evan der Meer, DennisMoreau, ClaraKaufmann, TobiasWalters, G BragiEllegaard, MariaAbdellaoui, AbdelAmes, DavidAmunts, KatrinAndersson, MicaelArmstrong, Nicola JBernard, ManonBlackburn, Nicholas BBlangero, JohnBoomsma, Dorret IBrodaty, HenryBrouwer, Rachel MBülow, RobinBøen, RuneCahn, WiepkeCalhoun, Vince DCaspers, SvenjaChing, Christopher R KCichon, SvenCiufolini, SimoneCrespo-Facorro, BenedictoCurran, Joanne EDale, Anders MDalvie, ShareefaDazzan, Paolade-Geus, Eco J Cde-Zubicaray, Greig Ide-Zwarte, Sonja M CDesrivieres, SylvaneDoherty, Joanne LDonohoe, GaryDraganski, BogdanEhrlich, StefanEising, ElseEspeseth, ThomasFejgin, KimFisher, Simon EFladby, TormodFrei, OleksandrFrouin, VincentFukunaga, MasakiGareau, ThomasGe, TianGlahn, David CGrabe, Hans JGroenewold, Nynke AGustafsson, OmarHaavik, JanHaberg, Asta KHall, JeremyHashimoto, RyotaHehir-Kwa, Jayne YHibar, Derrek PHillegers, Manon H JHoffmann, PerHolleran, LaurenaHolmes, Avram JHomuth, GeorgHottenga, Jouke-JanHulshoff-Pol, Hilleke EIkeda, MasashiJahanshad, NedaJockwitz, ChristianeJohansson, StefanJönsson, Erik GJørgensen, Niklas RKikuchi, MasatakaKnowles, Emma E MKumar, KuldeepLe-Hellard, StephanieLeu, CostinLinden, David E JLiu, JingyuLundervold, ArvidLundervold, Astri JohansenMaillard, Anne MMartin, Nicholas GMartin-Brevet, SandraMather, Karen AMathias, Samuel RMcMahon, Katie LMcRae, Allan FMedland, Sarah EMeyer-Lindenberg, AndreasMoberget, TorgeirModenato, ClaudiaMonereo-Sanchez, JenniferMorris, Derek WMühleisen, Thomas WMurray, Robin MNielsen, JacobNordvik, Jan ENyberg, LarsLoohuis, Loes M OldeOphoff, Roel AOwen, Michael JPaus, TomasPausova, ZdenkaPeralta, Juan MPike, G BrucePrieto, CarlosQuinlan, Erin BReinbold, Celine SMarques, Tiago ReisRucker, James J HSachdev, Perminder SSando, Sigrid BSchofield, Peter RSchork, Andrew JSchumann, GunterShin, JeanShumskaya, ElenaSilva, Ana ISisodiya, Sanjay MSteen, Vidar MStein, Dan JStrike, Lachlan TSuzuki, Ikuo KTamnes, Christian KTeumer, AlexanderThalamuthu, AnbupalamTordesillas-Gutierrez, DianaUhlmann, AnneUlfarsson, Magnus Ovan 't Ent, Dennisvan-den-Bree, Marianne B MVanderhaeghen, PierreVassos, EvangelosWen, WeiWittfeld, KatharinaWright, Margaret JAgartz, IngridDjurovic, SrdjanWestlye, Lars TStefansson, HreinnStefansson, KariJacquemont, SébastienThompson, Paul MAndreassen, Ole A2023-02-092023-02-092021-03-22Sønderby IE, van der Meer D, Moreau C, Kaufmann T, Walters GB, Ellegaard M,et al. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans. Transl Psychiatry. 2021 Mar 22;11(1):182.http://hdl.handle.net/10668/17384Low-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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Psychiatric disordersMolecular neuroscienceClinical geneticsBrainChromosome DeletionCognitionDNA Copy Number VariationsFemaleHumansMaleSchizophreniaresearch article33753722open accessEncéfaloDosificaciónTrastornos del neurodesarrolloCogniciónTrastorno autísticoPrevalenciaDiscapacidad intelectualImagen por resonancia magnéticaMegalencefaliaEsquizofrenia10.1038/s41398-021-01213-02158-3188PMC7985307https://www.nature.com/articles/s41398-021-01213-0.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307/pdf