1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Sønderby, I.E.; van der Meer, D.; Moreau, C.; Kaufmann, T.; Walters, G.B.; Ellegaard, M.; Abdellaoui, A.; Ames, D.; Amunts, K.; Andersson, M.; Armstrong, N.J.; Bernard, M.; Blackburn, N.B.; Blangero, J.; Boomsma, D.I.; Brodaty, H.; Brouwer, R.M.; Bülow, R.; Bøen, R.; Cahn, W.; Calhoun, V.D.; Caspers, S.; Ching, CRK; Cichon, S.; Ciufolini, S.; Crespo-Facorro, B.; Curran, J.E.; Dale, A.M.; Dalvie, S.; Dazzan, P.; de Geus, EJC; de Zubicaray, G.I.; de Zwarte, SMC; Desrivieres, S.; Doherty, J.L.; Donohoe, G.; Draganski, B.; Ehrlich, S.; Eising, E.; Espeseth, T.; Fejgin, K.; Fisher, S.E.; Fladby, T.; Frei, O.; Frouin, V.; Fukunaga, M.; Gareau, T.; Ge, T.; Glahn, D.C.; Grabe, H.J.; Groenewold, N.A.; Gústafsson, Ó.; Haavik, J.; Haberg, A.K.; Hall, J.; Hashimoto, R.; Hehir-Kwa, J.Y.; Hibar, D.P.; Hillegers, MHJ; Hoffmann, P.; Holleran, L.; Holmes, A.J.; Homuth, G.; Hottenga, J.J.; Hulshoff Pol, H.E.; Ikeda, M.; Jahanshad, N.; Jockwitz, C.; Johansson, S.; Jönsson, E.G.; Jørgensen, N.R.; Kikuchi, M.; Knowles, EEM; Kumar, K.; Le Hellard, S.; Leu, C.; Linden, DEJ; Liu, J.; Lundervold, A.; Lundervold, A.J.; Maillard, A.M.; Martin, N.G.; Martin-Brevet, S.; Mather, K.A.; Mathias, S.R.; McMahon, K.L.; McRae, A.F.; Medland, S.E.; Meyer-Lindenberg, A.; Moberget, T.; Modenato, C.; Sánchez, J.M.; Morris, D.W.; Mühleisen, T.W.; Murray, R.M.; Nielsen, J.; Nordvik, J.E.; Nyberg, L.; Loohuis, LMO; Ophoff, R.A.; Owen, M.J.; Paus, T.; Pausova, Z.; Peralta, J.M.; Pike, G.B.; Prieto, C.; Quinlan, E.B.; Reinbold, C.S.; Marques, T.R.; Rucker, JJH; Sachdev, P.S.; Sando, S.B.; Schofield, P.R.; Schork, A.J.; Schumann, G.; Shin, J.; Shumskaya, E.; Silva, A.I.; Sisodiya, S.M.; Steen, V.M.; Stein, D.J.; Strike, L.T.; Suzuki, I.K.; Tamnes, C.K.; Teumer, A.; Thalamuthu, A.; Tordesillas-Gutiérrez, D.; Uhlmann, A.; Ulfarsson, M.O.; van 't Ent, D.; van den Bree, MBM; Vanderhaeghen, P.; Vassos, E.; Wen, W.; Wittfeld, K.; Wright, M.J.; Agartz, I.; Djurovic, S.; Westlye, L.T.; Stefansson, H.; Stefansson, K.; Jacquemont, S.; Thompson, P.M.; Andreassen, O.A.

doi:10.1038/s41398-021-01213-0

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Details

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State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_89117CC8B7BA

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Journal

Translational psychiatry

Author(s)

Sønderby I.E., van der Meer D., Moreau C., Kaufmann T., Walters G.B., Ellegaard M., Abdellaoui A., Ames D., Amunts K., Andersson M., Armstrong N.J., Bernard M., Blackburn N.B., Blangero J., Boomsma D.I., Brodaty H., Brouwer R.M., Bülow R., Bøen R., Cahn W., Calhoun V.D., Caspers S., Ching CRK, Cichon S., Ciufolini S., Crespo-Facorro B., Curran J.E., Dale A.M., Dalvie S., Dazzan P., de Geus EJC, de Zubicaray G.I., de Zwarte SMC, Desrivieres S., Doherty J.L., Donohoe G., Draganski B., Ehrlich S., Eising E., Espeseth T., Fejgin K., Fisher S.E., Fladby T., Frei O., Frouin V., Fukunaga M., Gareau T., Ge T., Glahn D.C., Grabe H.J., Groenewold N.A., Gústafsson Ó., Haavik J., Haberg A.K., Hall J., Hashimoto R., Hehir-Kwa J.Y., Hibar D.P., Hillegers MHJ, Hoffmann P., Holleran L., Holmes A.J., Homuth G., Hottenga J.J., Hulshoff Pol H.E., Ikeda M., Jahanshad N., Jockwitz C., Johansson S., Jönsson E.G., Jørgensen N.R., Kikuchi M., Knowles EEM, Kumar K., Le Hellard S., Leu C., Linden DEJ, Liu J., Lundervold A., Lundervold A.J., Maillard A.M., Martin N.G., Martin-Brevet S., Mather K.A., Mathias S.R., McMahon K.L., McRae A.F., Medland S.E., Meyer-Lindenberg A., Moberget T., Modenato C., Sánchez J.M., Morris D.W., Mühleisen T.W., Murray R.M., Nielsen J., Nordvik J.E., Nyberg L., Loohuis LMO, Ophoff R.A., Owen M.J., Paus T., Pausova Z., Peralta J.M., Pike G.B., Prieto C., Quinlan E.B., Reinbold C.S., Marques T.R., Rucker JJH, Sachdev P.S., Sando S.B., Schofield P.R., Schork A.J., Schumann G., Shin J., Shumskaya E., Silva A.I., Sisodiya S.M., Steen V.M., Stein D.J., Strike L.T., Suzuki I.K., Tamnes C.K., Teumer A., Thalamuthu A., Tordesillas-Gutiérrez D., Uhlmann A., Ulfarsson M.O., van 't Ent D., van den Bree MBM, Vanderhaeghen P., Vassos E., Wen W., Wittfeld K., Wright M.J., Agartz I., Djurovic S., Westlye L.T., Stefansson H., Stefansson K., Jacquemont S., Thompson P.M., Andreassen O.A.

Working group(s)

ENIGMA-CNV working group

Contributor(s)

van der Meer D., de Geus EJC, de Zubicaray G.I., de Zwarte SMC, Le Hellard S., van 't Ent D., van den Bree MBM

ISSN

2158-3188 (Electronic)

ISSN-L

2158-3188

Publication state

Published

Issued date

22/03/2021

Peer-reviewed

Oui

Volume

Number

Pages

182

Language

english

Notes

Publication types: Journal Article
Publication Status: epublish

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.

URN

urn:nbn:ch:serval-BIB_89117CC8B7BA6

OAI-PMH

oai:serval.unil.ch:BIB_89117CC8B7BA

DOI

10.1038/s41398-021-01213-0

Pubmed

33753722

Web of science

000632961500003

Open Access

Yes