| Title: | Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis |
| Journal: | Communications Biology |
| Published: | 23 Apr 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32327693/ |
| DOI: | https://doi.org/10.1038/s42003-020-0921-5 |
| URL: | https://www.nature.com/articles/s42003-020-0921-5.pdf |
Publication 9110
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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.</p>
38 Authors
- Gudjon R. Oskarsson
- Asmundur Oddsson
- Magnus K. Magnusson
- Ragnar P. Kristjansson
- Gisli H. Halldorsson
- Egil Ferkingstad
- Florian Zink
- Anna Helgadottir
- Erna V. Ivarsdottir
- Gudny A. Arnadottir
- Brynjar O. Jensson
- Hildigunnur Katrinardottir
- Gardar Sveinbjornsson
- Anna M. Kristinsdottir
- Amy L. Lee
- Jona Saemundsdottir
- Lilja Stefansdottir
- Jon K. Sigurdsson
- Olafur B. Davidsson
- Stefania Benonisdottir
- Aslaug Jonasdottir
- Adalbjorg Jonasdottir
- Stefan Jonsson
- Reynir L. Gudmundsson
- Folkert W. Asselbergs
- Vinicius Tragante
- Bjarni Gunnarsson
- Gisli Masson
- Gudmar Thorleifsson
- Thorunn Rafnar
- Hilma Holm
- Isleifur Olafsson
- Pall T. Onundarson
- Daniel F. Gudbjartsson
- Gudmundur L. Norddahl
- Unnur Thorsteinsdottir
- Patrick Sulem
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 24711 | On the quest for tissue-specific contributions to disease |
Enabling scientific discoveries that improve human health