Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis
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,...
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ftucl:oai:eprints.ucl.ac.uk.OAI2:10105372 2023-12-24T10:17:53+01:00 Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis Oskarsson, GR Oddsson, A Magnusson, MK Kristjansson, RP Halldorsson, GH Ferkingstad, E Zink, F Helgadottir, A Ivarsdottir, EV Arnadottir, GA Jensson, BO Katrinardottir, H Sveinbjornsson, G Kristinsdottir, AM Lee, AL Saemundsdottir, J Stefansdottir, L Sigurdsson, JK Davidsson, OB Benonisdottir, S Jonasdottir, A Jonsson, S Gudmundsson, RL Asselbergs, FW Tragante, V Gunnarsson, B Masson, G Thorleifsson, G Rafnar, T Holm, H Olafsson, I Onundarson, PT Gudbjartsson, DF Norddahl, GL Thorsteinsdottir, U Sulem, P Stefansson, K 2020-04-23 text https://discovery.ucl.ac.uk/id/eprint/10105372/1/s42003-020-0921-5.pdf https://discovery.ucl.ac.uk/id/eprint/10105372/ eng eng NATURE PUBLISHING GROUP https://discovery.ucl.ac.uk/id/eprint/10105372/1/s42003-020-0921-5.pdf https://discovery.ucl.ac.uk/id/eprint/10105372/ open Communications Biology , 3 (1) , Article 189. (2020) Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics IRON REGULATORY PROTEIN-1 GENETIC-VARIATION HIGH-RISK VARIANTS HOMEOSTASIS DISEASE BINDING MODEL POWER LOCI Article 2020 ftucl 2023-11-27T13:07:26Z 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. Article in Journal/Newspaper Iceland University College London: UCL Discovery |
institution |
Open Polar |
collection |
University College London: UCL Discovery |
op_collection_id |
ftucl |
language |
English |
topic |
Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics IRON REGULATORY PROTEIN-1 GENETIC-VARIATION HIGH-RISK VARIANTS HOMEOSTASIS DISEASE BINDING MODEL POWER LOCI |
spellingShingle |
Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics IRON REGULATORY PROTEIN-1 GENETIC-VARIATION HIGH-RISK VARIANTS HOMEOSTASIS DISEASE BINDING MODEL POWER LOCI Oskarsson, GR Oddsson, A Magnusson, MK Kristjansson, RP Halldorsson, GH Ferkingstad, E Zink, F Helgadottir, A Ivarsdottir, EV Arnadottir, GA Jensson, BO Katrinardottir, H Sveinbjornsson, G Kristinsdottir, AM Lee, AL Saemundsdottir, J Stefansdottir, L Sigurdsson, JK Davidsson, OB Benonisdottir, S Jonasdottir, A Jonsson, S Gudmundsson, RL Asselbergs, FW Tragante, V Gunnarsson, B Masson, G Thorleifsson, G Rafnar, T Holm, H Olafsson, I Onundarson, PT Gudbjartsson, DF Norddahl, GL Thorsteinsdottir, U Sulem, P Stefansson, K Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
topic_facet |
Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics IRON REGULATORY PROTEIN-1 GENETIC-VARIATION HIGH-RISK VARIANTS HOMEOSTASIS DISEASE BINDING MODEL POWER LOCI |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Oskarsson, GR Oddsson, A Magnusson, MK Kristjansson, RP Halldorsson, GH Ferkingstad, E Zink, F Helgadottir, A Ivarsdottir, EV Arnadottir, GA Jensson, BO Katrinardottir, H Sveinbjornsson, G Kristinsdottir, AM Lee, AL Saemundsdottir, J Stefansdottir, L Sigurdsson, JK Davidsson, OB Benonisdottir, S Jonasdottir, A Jonsson, S Gudmundsson, RL Asselbergs, FW Tragante, V Gunnarsson, B Masson, G Thorleifsson, G Rafnar, T Holm, H Olafsson, I Onundarson, PT Gudbjartsson, DF Norddahl, GL Thorsteinsdottir, U Sulem, P Stefansson, K |
author_facet |
Oskarsson, GR Oddsson, A Magnusson, MK Kristjansson, RP Halldorsson, GH Ferkingstad, E Zink, F Helgadottir, A Ivarsdottir, EV Arnadottir, GA Jensson, BO Katrinardottir, H Sveinbjornsson, G Kristinsdottir, AM Lee, AL Saemundsdottir, J Stefansdottir, L Sigurdsson, JK Davidsson, OB Benonisdottir, S Jonasdottir, A Jonsson, S Gudmundsson, RL Asselbergs, FW Tragante, V Gunnarsson, B Masson, G Thorleifsson, G Rafnar, T Holm, H Olafsson, I Onundarson, PT Gudbjartsson, DF Norddahl, GL Thorsteinsdottir, U Sulem, P Stefansson, K |
author_sort |
Oskarsson, GR |
title |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
title_short |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
title_full |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
title_fullStr |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
title_full_unstemmed |
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
title_sort |
predicted loss and gain of function mutations in aco1 are associated with erythropoiesis |
publisher |
NATURE PUBLISHING GROUP |
publishDate |
2020 |
url |
https://discovery.ucl.ac.uk/id/eprint/10105372/1/s42003-020-0921-5.pdf https://discovery.ucl.ac.uk/id/eprint/10105372/ |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Communications Biology , 3 (1) , Article 189. (2020) |
op_relation |
https://discovery.ucl.ac.uk/id/eprint/10105372/1/s42003-020-0921-5.pdf https://discovery.ucl.ac.uk/id/eprint/10105372/ |
op_rights |
open |
_version_ |
1786206302898225152 |