TY - JOUR
T1 - Effects of copy number variations on brain structure and risk for psychiatric illness
T2 - Large-scale studies from the ENIGMA working groups on CNVs
AU - for the ENIGMA-CNV Working Group
AU - for the ENIGMA 22q11.2 Deletion Syndrome Working Group
AU - Sønderby, Ida E.
AU - Ching, Christopher R.K.
AU - Thomopoulos, Sophia I.
AU - van der Meer, Dennis
AU - Sun, Daqiang
AU - Villalon-Reina, Julio E.
AU - Agartz, Ingrid
AU - Amunts, Katrin
AU - Arango, Celso
AU - Armstrong, Nicola J.
AU - Ayesa-Arriola, Rosa
AU - Bakker, Geor
AU - Bassett, Anne S.
AU - Boomsma, Dorret I.
AU - Bülow, Robin
AU - Butcher, Nancy J.
AU - Calhoun, Vince D.
AU - Caspers, Svenja
AU - Chow, Eva W.C.
AU - Cichon, Sven
AU - Ciufolini, Simone
AU - Craig, Michael C.
AU - Crespo-Facorro, Benedicto
AU - Cunningham, Adam C.
AU - Dale, Anders M.
AU - Dazzan, Paola
AU - de Zubicaray, Greig I.
AU - Djurovic, Srdjan
AU - Doherty, Joanne L.
AU - Donohoe, Gary
AU - Draganski, Bogdan
AU - Durdle, Courtney A.
AU - Ehrlich, Stefan
AU - Emanuel, Beverly S.
AU - Espeseth, Thomas
AU - Fisher, Simon E.
AU - Ge, Tian
AU - Glahn, David C.
AU - Grabe, Hans J.
AU - Gur, Raquel E.
AU - Gutman, Boris A.
AU - Haavik, Jan
AU - Håberg, Asta K.
AU - Hansen, Laura A.
AU - Hashimoto, Ryota
AU - Hibar, Derrek P.
AU - Holmes, Avram J.
AU - Hottenga, Jouke Jan
AU - Hulshoff Pol, Hilleke E.
AU - Jalbrzikowski, Maria
N1 - Publisher Copyright:
© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - brain structural imaging
KW - copy number variant
KW - diffusion tensor imaging
KW - evolution
KW - genetics-first approach
KW - neurodevelopmental disorders
KW - psychiatric disorders
UR - https://www.scopus.com/pages/publications/85101270199
U2 - 10.1002/hbm.25354
DO - 10.1002/hbm.25354
M3 - Review article
C2 - 33615640
AN - SCOPUS:85101270199
SN - 1065-9471
VL - 43
SP - 300
EP - 328
JO - Human Brain Mapping
JF - Human Brain Mapping
IS - 1
ER -