dc.contributor |
Háskóli Íslands (HÍ) |
dc.contributor |
University of Iceland (UI) |
dc.contributor.author |
Walters, G. Bragi |
dc.contributor.author |
Gústafsson, Ómar |
dc.contributor.author |
Sveinbjornsson, Gardar |
dc.contributor.author |
Eiriksdottir, Valgerdur Kristin |
dc.contributor.author |
Ágústsdóttir, Arna B. |
dc.contributor.author |
Jónsdóttir, Guðrún A. |
dc.contributor.author |
Steinberg, Stacy |
dc.contributor.author |
Gunnarsson, Árni F. |
dc.contributor.author |
Magnússon, Magnús I. |
dc.contributor.author |
Unnsteinsdóttir, Unnur |
dc.contributor.author |
Lee, Amy L. |
dc.contributor.author |
Jónasdóttir, Aðalbjörg |
dc.contributor.author |
Sigurðsson, Ásgeir |
dc.contributor.author |
Jónasdóttir, Áslaug |
dc.contributor.author |
Skúladóttir, Ástrós |
dc.contributor.author |
Jonsson, Lina |
dc.contributor.author |
Nawaz, Muhammad S. |
dc.contributor.author |
sulem, patrick |
dc.contributor.author |
Frigge, Mike |
dc.contributor.author |
Ingason, Andrés |
dc.contributor.author |
Love, Askell |
dc.contributor.author |
Norðdahl, Guðmundur L. |
dc.contributor.author |
Zervas, Mark |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Ulfarsson, Magnus |
dc.contributor.author |
Sæmundsen, Evald E. |
dc.contributor.author |
Stefansson, Hreinn |
dc.contributor.author |
Stefansson, Kari |
dc.date.accessioned |
2019-12-16T10:57:30Z |
dc.date.available |
2019-12-16T10:57:30Z |
dc.date.issued |
2018-08-27 |
dc.identifier.citation |
Walters, G.B., Gustafsson, O., Sveinbjornsson, G. et al. MAP1B mutations cause intellectual disability and extensive white matter deficit. Nat Commun 9, 3456 (2018) doi:10.1038/s41467-018-05595-6 |
dc.identifier.issn |
2041-1723 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1390 |
dc.description |
Publisher's version (útgefin grein).
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations. |
dc.description.abstract |
Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an
important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in
microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree
(genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and
R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter
(WM) volume (β = −2.1SD, P = 5.1 × 10−8), 47% less corpus callosum (CC) volume (β =
−2.4SD, P = 5.5 × 10−10) and lower brain-wide fractional anisotropy (P = 6.7 × 10−4). In
summary, we show that loss of MAP1B function affects general cognitive ability through a
profound, brain-wide WM deficit with likely disordered or compromised axons. |
dc.description.sponsorship |
We are grateful to the participants and we thank the psychologists, nurses and staff, in
particular Berglind Eiriksdottir, at the Research Recruitment Center and technicians and
staff at Röntgen Domus. We also thank the staff at deCODE genetics core facilities and
all our colleagues for their important contribution to this work. L.J. received support
from the Swedish Society of Medicine, the Swedish Brain Foundation and Swedish
Society for Medical Research. The research leading to these results has received support
from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no.
115008 (NEWMEDS) and no. 115300 (EUAIMS) of which resources are composed of
EFPIA in-kind contribution and financial contribution from the European Union’s
Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7 funded grant no. 602450
(IMAGEMEND) and EU funded FP7-People-2011-IAPP grant agreement no. 286213
(PsychDPC). |
dc.format.extent |
3456 |
dc.language.iso |
en |
dc.publisher |
Springer Science and Business Media LLC |
dc.relation |
info:eu-repo/grantAgreement/EC/FP7/602450 |
dc.relation |
info:eu-repo/grantAgreement/EC/FP7/286213 |
dc.relation.ispartofseries |
Nature Communications;9(1) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Developmental disorders |
dc.subject |
Genetics of the nervous system |
dc.subject |
Magnetic resonance imaging |
dc.subject |
Medical genetics |
dc.subject |
Þroskafrávik |
dc.subject |
Taugakerfi |
dc.subject |
Erfðafræði |
dc.subject |
Læknisfræði |
dc.title |
MAP1B mutations cause intellectual disability and extensive white matter deficit |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Nature Communications |
dc.identifier.doi |
10.1038/s41467-018-05595-6 |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Electrical and Computer Engineering (UI) |
dc.contributor.department |
Rafmagns- og tölvuverkfræðideild (HÍ) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |