Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs. Issue 1 (21st February 2021)

• Record Type: Journal Article
• Authors: Sønderby, Ida E.; Ching, Christopher R. K.; Thomopoulos, Sophia I.; van der Meer, Dennis; Sun, Daqiang; Villalon‐Reina, Julio E.; Agartz, Ingrid; Amunts, Katrin; Arango, Celso; Armstrong, Nicola J.; Ayesa‐Arriola, Rosa; Bakker, Geor; Bassett, Anne S.; Boomsma, Dorret I.; Bülow, Robin; Butcher, Nancy J.; Calhoun, Vince D.; Caspers, Svenja; Chow, Eva W. C.; Cichon, Sven; Ciufolini, Simone; Craig, Michael C.; Crespo‐Facorro, Benedicto; Cunningham, Adam C.; Dale, Anders M.; Dazzan, Paola; de Zubicaray, Greig I.; Djurovic, Srdjan; Doherty, Joanne L.; Donohoe, Gary; Draganski, Bogdan; Durdle, Courtney A.; Ehrlich, Stefan; Emanuel, Beverly S.; Espeseth, Thomas; Fisher, Simon E.; Ge, Tian; Glahn, David C.; Grabe, Hans J.; Gur, Raquel E.; Gutman, Boris A.; Haavik, Jan; Håberg, Asta K.; Hansen, Laura A.; Hashimoto, Ryota; Hibar, Derrek P.; Holmes, Avram J.; Hottenga, Jouke‐Jan; Hulshoff Pol, Hilleke E.; Jalbrzikowski, Maria; Knowles, Emma E. M.; Kushan, Leila; Linden, David E. J.; Liu, Jingyu; Lundervold, Astri J.; Martin‐Brevet, Sandra; Martínez, Kenia; Mather, Karen A.; Mathias, Samuel R.; McDonald‐McGinn, Donna M.; McRae, Allan F.; Medland, Sarah E.; Moberget, Torgeir; Modenato, Claudia; Monereo Sánchez, Jennifer; Moreau, Clara A.; Mühleisen, Thomas W.; Paus, Tomas; Pausova, Zdenka; Prieto, Carlos; Ragothaman, Anjanibhargavi; Reinbold, Céline S.; Reis Marques, Tiago; Repetto, Gabriela M.; Reymond, Alexandre; Roalf, David R.; Rodriguez‐Herreros, Borja; Rucker, James J.; Sachdev, Perminder S.; Schmitt, James E.; Schofield, Peter R.; Silva, Ana I.; Stefansson, Hreinn; Stein, Dan J.; Tamnes, Christian K.; Tordesillas‐Gutiérrez, Diana; Ulfarsson, Magnus O.; Vajdi, Ariana; van 't Ent, Dennis; van den Bree, Marianne B. M.; Vassos, Evangelos; Vázquez‐Bourgon, Javier; Vila‐Rodriguez, Fidel; Walters, G. Bragi; Wen, Wei; Westlye, Lars T.; Wittfeld, Katharina; Zackai, Elaine H.; Stefánsson, Kári; Jacquemont, Sebastien; Thompson, Paul M.; Bearden, Carrie E.; Andreassen, Ole A.;
• Other Names: Bernard Manon investigator.; Blackburn Nicholas B. investigator.; Bøen Rune investigator.; de Geus Eco investigator.; de Zwarte Sonja M. C. investigator.; Forti Marta Di investigator.; Frei Oleksandr investigator.; Fukunaga Masaki investigator.; Hehir‐Kwa Jayne Y. investigator.; Hillegers Manon H. J. investigator.; Hoffmann Per investigator.; Homuth Georg investigator.; Jahanshad Neda investigator.; Koops Sanne investigator.; Kumar Kuldeep investigator.; Kikuchi Masataka investigator.; Le Hellard Stephanie investigator.; Leu Costin investigator.; Murray Robin M investigator.; Nærland Terje investigator.; Nyberg Lars investigator.; Ophoff Roel A. investigator.; Pike G Bruce investigator.; Sando Sigrid B. investigator.; Shin Jean investigator.; Shumskaya Elena investigator.; Sisodiya Sanjay M. investigator.; Steen Vidar M. investigator.; Teumer Alexander investigator.; Uhlmann Anne investigator.; Wright Margaret J. investigator.; Antshel Kevin M. investigator.; Campbell Linda E. investigator.; Crossley Nicolas A. investigator.; Crowley T. Blaine investigator.; Daly Eileen investigator.; Fiksinski Ania M. investigator.; Forsyth Jennifer K. investigator.; Fremont Wanda investigator.; Goodrich‐Hunsaker Naomi J. investigator.; Gudbrandsen Maria investigator.; Jonas Rachel K. investigator.; Kates Wendy R. investigator.; Lin Amy investigator.; McCabe Kathryn L. investigator.; Moss Hayley investigator.; Murphy Declan G. investigator.; Murphy Kieran C. investigator.; Owen Michael J. investigator.; Ruparel Kosha investigator.; Simon Tony. J. investigator.; van Amelsvoort Therese investigator.; Vorstman Jacob A. S. investigator.; Thompson P.M. guestEditor.; Jahanshad N. guestEditor.; Schmaal L. guestEditor.; Turner J.A. guestEditor.; Winkler A. guestEditor.; Thomopoulos S.I. guestEditor.; Egan G.F. guestEditor.; Kochunov P. guestEditor.;
• Is Part Of: Human brain mapping. Volume 43:Issue 1(2022)
• Page Start: 300
• Page End: 328
• Publication Date: 2021-02-21
• Subjects: brain structural imaging -- copy number variant -- diffusion tensor imaging -- evolution -- genetics‐first approach -- neurodevelopmental disorders -- psychiatric disorders; Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.25354
• Languages: English
• ISSNs: 1065-9471

Abstract

Abstract: The 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. Abstract : The enhancing neuroimaging genetics through meta‐analysis (ENIGMA) copy number variant (CNV) and 22q11.2 Working Groups focus on gaining insight into how rare genetic variants affect human brain development, cognition, and behavior. The two ENIGMA working groups have collated CNV and brain‐imaging data from numerous individuals, gathered by numerous international research centers, and analyzed this data with standardized processing and analysis pipelines. Future directions for the ENIGMA CNV and 22q11.2 working groups are to analyze CNVs with larger sample sizes and more imaging modalities to better understand how rare genetic variants affect the brain, and their clinical and behavioral consequences.