| Literature DB >> 33753722 |
Ida E Sønderby1,2,3, Dennis van der Meer4,5, Clara Moreau6,7, Tobias Kaufmann4,8, G Bragi Walters9,10, Maria Ellegaard11, Abdel Abdellaoui12,13, David Ames14,15, Katrin Amunts16,17, Micael Andersson18,19, Nicola J Armstrong20, Manon Bernard21, Nicholas B Blackburn22, John Blangero22, Dorret I Boomsma13,23,24, Henry Brodaty25,26, Rachel M Brouwer27, Robin Bülow28, Rune Bøen4,29, Wiepke Cahn27,30, Vince D Calhoun31,32, Svenja Caspers16,33, Christopher R K Ching34, Sven Cichon16,35,36, Simone Ciufolini37, Benedicto Crespo-Facorro38,39, Joanne E Curran22, Anders M Dale40, Shareefa Dalvie41, Paola Dazzan42, Eco J C de Geus13,23,24, Greig I de Zubicaray43, Sonja M C de Zwarte27, Sylvane Desrivieres44, Joanne L Doherty45,46, Gary Donohoe47, Bogdan Draganski48,49, Stefan Ehrlich50, Else Eising51, Thomas Espeseth52,53, Kim Fejgin54, Simon E Fisher51,55, Tormod Fladby56,57, Oleksandr Frei4, Vincent Frouin58, Masaki Fukunaga59,60, Thomas Gareau58, Tian Ge61,62,63, David C Glahn64,65,66, Hans J Grabe67,68, Nynke A Groenewold41, Ómar Gústafsson9, Jan Haavik69,70, Asta K Haberg71,72, Jeremy Hall45,73, Ryota Hashimoto74,75, Jayne Y Hehir-Kwa76, Derrek P Hibar77, Manon H J Hillegers78, Per Hoffmann36,79, Laurena Holleran47, Avram J Holmes80,81,82, Georg Homuth83, Jouke-Jan Hottenga13,23,24, Hilleke E Hulshoff Pol27, Masashi Ikeda84, Neda Jahanshad34, Christiane Jockwitz16,33, Stefan Johansson85,86, Erik G Jönsson87,88, Niklas R Jørgensen89,90, Masataka Kikuchi91, Emma E M Knowles64,66, Kuldeep Kumar6, Stephanie Le Hellard92,93, Costin Leu63,94,95,96, David E J Linden5,45, Jingyu Liu31, Arvid Lundervold69,97, Astri Johansen Lundervold98, Anne M Maillard99, Nicholas G Martin100, Sandra Martin-Brevet48, Karen A Mather25,101, Samuel R Mathias64,66, Katie L McMahon102, Allan F McRae103,104, Sarah E Medland105, Andreas Meyer-Lindenberg106, Torgeir Moberget4,52, Claudia Modenato48,107, Jennifer Monereo Sánchez108,109, Derek W Morris47, Thomas W Mühleisen16,17,35, Robin M Murray110, Jacob Nielsen54, Jan E Nordvik111, Lars Nyberg18,19,112, Loes M Olde Loohuis113, Roel A Ophoff113,114, Michael J Owen45, Tomas Paus115,116, Zdenka Pausova21,116, Juan M Peralta22, G Bruce Pike117, Carlos Prieto118, Erin B Quinlan119, Céline S Reinbold35,36,52, Tiago Reis Marques120,121, James J H Rucker122, Perminder S Sachdev25,123, Sigrid B Sando71,124, Peter R Schofield125,126, Andrew J Schork127,128, Gunter Schumann119, Jean Shin21,116, Elena Shumskaya55,129, Ana I Silva5,45,46, Sanjay M Sisodiya94,96, Vidar M Steen92,93, Dan J Stein130, Lachlan T Strike104, Ikuo K Suzuki131,132,133, Christian K Tamnes4,134,135, Alexander Teumer136, Anbupalam Thalamuthu25, Diana Tordesillas-Gutiérrez38,137, Anne Uhlmann41, Magnus O Ulfarsson9,138, Dennis van 't Ent13,23, Marianne B M van den Bree45,73, Pierre Vanderhaeghen139,140,141, Evangelos Vassos110,142, Wei Wen25, Katharina Wittfeld67,68, Margaret J Wright104,143, Ingrid Agartz87,88,135, Srdjan Djurovic29,92, Lars T Westlye4,144,52, Hreinn Stefansson9, Kari Stefansson9,10, Sébastien Jacquemont6,145, Paul M Thompson34, Ole A Andreassen4.
Abstract
Low-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.Entities:
Mesh：
Year: 2021 PMID： 33753722 PMCID： PMC7985307 DOI： 10.1038/s41398-021-01213-0
Source DB: PubMed Journal: Transl Psychiatry ISSN： 2158-3188 Impact factor: 7.989