Hum Brain Mapp. 2021 Feb 21. doi: 10.1002/hbm.25354. Online ahead of print.
Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs
Ida E Sønderby 1 2 3, Christopher R K Ching 4, Sophia I Thomopoulos 4, Dennis van der Meer 2 5, Daqiang Sun 6 7, Julio E Villalon-Reina 4, Ingrid Agartz 8 9 10, Katrin Amunts 11 12, Celso Arango 13 14, Nicola J Armstrong 15, Rosa Ayesa-Arriola 14 16, Geor Bakker 17 18, Anne S Bassett 19 20 21, Dorret I Boomsma 22 23, Robin Bülow 24, Nancy J Butcher 21 25, Vince D Calhoun 26, Svenja Caspers 11 27, Eva W C Chow 19 21, Sven Cichon 11 28 29, Simone Ciufolini 30, Michael C Craig 31, Benedicto Crespo-Facorro 32, Adam C Cunningham 33, Anders M Dale 34 35, Paola Dazzan 36, Greig I de Zubicaray 37, Srdjan Djurovic 1 38, Joanne L Doherty 33 39, Gary Donohoe 40, Bogdan Draganski 41 42, Courtney A Durdle 43, Stefan Ehrlich 44, Beverly S Emanuel 45, Thomas Espeseth 46 47, Simon E Fisher 48 49, Tian Ge 50 51, David C Glahn 52 53, Hans J Grabe 54 55, Raquel E Gur 56 57, Boris A Gutman 58, Jan Haavik 59 60, Asta K Håberg 61 62, Laura A Hansen 63, Ryota Hashimoto 64 65, Derrek P Hibar 66, Avram J Holmes 67 68, Jouke-Jan Hottenga 22, Hilleke E Hulshoff Pol 69, Maria Jalbrzikowski 70, Emma E M Knowles 51 71, Leila Kushan 72, David E J Linden 73 74, Jingyu Liu 26 75, Astri J Lundervold 76, Sandra Martin-Brevet 41, Kenia Martínez 13 14 77, Karen A Mather 78 79, Samuel R Mathias 53 71, Donna M McDonald-McGinn 45 80 81, Allan F McRae 82, Sarah E Medland 83, Torgeir Moberget 84, Claudia Modenato 41 85, Jennifer Monereo Sánchez 73 86 87, Clara A Moreau 88, Thomas W Mühleisen 11 12 29, Tomas Paus 89 90, Zdenka Pausova 91, Carlos Prieto 92, Anjanibhargavi Ragothaman 93, Céline S Reinbold 29 94, Tiago Reis Marques 30 95, Gabriela M Repetto 96, Alexandre Reymond 97, David R Roalf 56, Borja Rodriguez-Herreros 98, James J Rucker 36, Perminder S Sachdev 78 99, James E Schmitt 100, Peter R Schofield 79 101, Ana I Silva 74 102, Hreinn Stefansson 103, Dan J Stein 104, Christian K Tamnes 2 9 105, Diana Tordesillas-Gutiérrez 14 106, Magnus O Ulfarsson 103 107, Ariana Vajdi 72, Dennis van ‘t Ent 22, Marianne B M van den Bree 33, Evangelos Vassos 108, Javier Vázquez-Bourgon 14 16 109, Fidel Vila-Rodriguez 110, G Bragi Walters 103 111, Wei Wen 78, Lars T Westlye 3 46 112, Katharina Wittfeld 54 55, Elaine H Zackai 45 80, Kári Stefánsson 103 111, Sebastien Jacquemont 88 113, Paul M Thompson 4, Carrie E Bearden 6 114, Ole A Andreassen 2, ENIGMA-CNV Working Group; ENIGMA 22q11.2 Deletion Syndrome Working GroupAffiliations expand
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.
- PMID: 33615640
- DOI: 10.1002/hbm.25354