Sønderby, Ida EChing, Christopher R KThomopoulos, Sophia Ivan der Meer, DennisSun, DaqiangVillalon-Reina, Julio EAgartz, IngridAmunts, KatrinArango, CelsoArmstrong, Nicola JAyesa-Arriola, RosaBakker, GeorBassett, Anne SBoomsma, Dorret IBülow, RobinButcher, Nancy JCalhoun, Vince DCaspers, SvenjaChow, Eva W CCichon, SvenCiufolini, SimoneCraig, Michael CCrespo-Facorro, BenedictoCunningham, Adam CDale, Anders MDazzan, Paolade Zubicaray, Greig IDjurovic, SrdjanDoherty, Joanne LDonohoe, GaryDraganski, BogdanDurdle, Courtney AEhrlich, StefanEmanuel, Beverly SEspeseth, ThomasFisher, Simon EGe, TianGlahn, David CGrabe, Hans JGur, Raquel EGutman, Boris AHaavik, JanHåberg, Asta KHansen, Laura AHashimoto, RyotaHibar, Derrek PHolmes, Avram JHottenga, Jouke-JanHulshoff Pol, Hilleke EJalbrzikowski, MariaKnowles, Emma E MKushan, LeilaLinden, David E JLiu, JingyuLundervold, Astri JMartin-Brevet, SandraMartínez, KeniaMather, Karen AMathias, Samuel RMcDonald-McGinn, Donna MMcRae, Allan FMedland, Sarah EMoberget, TorgeirModenato, ClaudiaMonereo Sánchez, JenniferMoreau, Clara AMühleisen, Thomas WPaus, TomasPausova, ZdenkaPrieto, CarlosRagothaman, AnjanibhargaviReinbold, Céline SReis Marques, TiagoRepetto, Gabriela MReymond, AlexandreRoalf, David RRodriguez-Herreros, BorjaRucker, James JSachdev, Perminder SSchmitt, James ESchofield, Peter RSilva, Ana IStefansson, HreinnStein, Dan JTamnes, Christian KTordesillas-Gutiérrez, DianaUlfarsson, Magnus OVajdi, Arianavan 't Ent, Dennisvan den Bree, Marianne B MVassos, EvangelosVázquez-Bourgon, JavierVila-Rodriguez, FidelWalters, G BragiWen, WeiWestlye, Lars TWittfeld, KatharinaZackai, Elaine HStefánsson, KáriJacquemont, SebastienThompson, Paul MBearden, Carrie EAndreassen, Ole AENIGMA-CNV Working GroupENIGMA 22q11.2 Deletion Syndrome Working Group2023-02-092023-02-092021-02-21http://hdl.handle.net/10668/17215The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/brain structural imagingcopy number variantdiffusion tensor imagingevolutiongenetics-first approachneurodevelopmental disorderspsychiatric disordersBrainDNA Copy Number VariationsHumansMagnetic Resonance ImagingMental DisordersMulticenter Studies as TopicNeurodevelopmental DisordersNeuroimagingresearch article33615640open access10.1002/hbm.253541097-0193PMC8675420https://eprints.qut.edu.au/209970/1/82772709.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675420/pdf