dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Óskarsson, Guðjón R. |
dc.contributor.author |
Oddsson, Asmundur |
dc.contributor.author |
Magnusson, Magnus Karl |
dc.contributor.author |
Kristjansson, Ragnar |
dc.contributor.author |
Halldorsson, Gisli |
dc.contributor.author |
Ferkingstad, Egil |
dc.contributor.author |
Zink, Florian |
dc.contributor.author |
Helgadottir, Anna |
dc.contributor.author |
Ívarsdóttir, Erna V. |
dc.contributor.author |
Arnadottir, Gudny |
dc.contributor.author |
Jensson, Brynjar Örn |
dc.contributor.author |
Katrinardottir, Hildigunnur |
dc.contributor.author |
Sveinbjornsson, Gardar |
dc.contributor.author |
Kristinsdóttir, Anna Margrét |
dc.contributor.author |
Lee, Amy L. |
dc.contributor.author |
Sæmundsdóttir, Jóna |
dc.contributor.author |
Stefánsdóttir, Lilja |
dc.contributor.author |
Sigurðsson, Jón K. |
dc.contributor.author |
Davíðsson, Ólafur B. |
dc.contributor.author |
Benonisdottir, Stefania |
dc.contributor.author |
Jónasdóttir, Áslaug |
dc.contributor.author |
Jónasdóttir, Aðalbjörg |
dc.contributor.author |
Jonsson, Stefan |
dc.contributor.author |
Guðmundsson, Reynir L. |
dc.contributor.author |
Asselbergs, Folkert W. |
dc.contributor.author |
Tragante, Vinicius |
dc.contributor.author |
Gunnarsson, Bjarni |
dc.contributor.author |
Másson, Gísli |
dc.contributor.author |
Thorleifsson, Gudmar |
dc.contributor.author |
Rafnar, Thorunn |
dc.contributor.author |
Holm, Hilma |
dc.contributor.author |
Olafsson, Isleifur |
dc.contributor.author |
Önundarson, Páll Torfi |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Norðdahl, Guðmundur L. |
dc.contributor.author |
Thorsteinsdottir, Unnur |
dc.contributor.author |
sulem, patrick |
dc.contributor.author |
Stefansson, Kari |
dc.date.accessioned |
2020-10-30T13:26:38Z |
dc.date.available |
2020-10-30T13:26:38Z |
dc.date.issued |
2020-04-23 |
dc.identifier.citation |
Oskarsson, G.R., Oddsson, A., Magnusson, M.K. et al. Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis. Communications Biology 3, 189 (2020). https://doi.org/10.1038/s42003-020-0921-5 |
dc.identifier.issn |
2399-3642 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/2151 |
dc.description |
Publisher's version (útgefin grein) |
dc.description.abstract |
Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = −1.61 SD, CI95 = [−1.98, −1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10−14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration. |
dc.description.sponsorship |
We thank the individuals who participated in this study and whose contributions made this work possible. We also thank our valued colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK Biobank Resource under application number 24711. F.W.A. is supported by UCL Hospitals NIHR Biomedical Research Centre. |
dc.format.extent |
189 |
dc.language.iso |
en |
dc.publisher |
Springer Science and Business Media LLC |
dc.relation.ispartofseries |
Communications Biology;3(1) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Hemoglobin |
dc.subject |
ACO1 |
dc.subject |
Genome-wide |
dc.subject |
Blóðrannsóknir |
dc.subject |
Erfðarannsóknir |
dc.subject |
Gen |
dc.title |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
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 |
Communications Biology |
dc.identifier.doi |
10.1038/s42003-020-0921-5 |
dc.relation.url |
https://www.nature.com/articles/s42003-020-0921-5 |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |