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GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility
Autoimmune Addison’s disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2021
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878795/ https://www.ncbi.nlm.nih.gov/pubmed/33574239 http://dx.doi.org/10.1038/s41467-021-21015-8 |
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| author | Eriksson, Daniel Røyrvik, Ellen Christine Aranda-Guillén, Maribel Berger, Amund Holte Landegren, Nils Artaza, Haydee Hallgren, Åsa Grytaas, Marianne Aardal Ström, Sara Bratland, Eirik Botusan, Ileana Ruxandra Oftedal, Bergithe Eikeland Breivik, Lars Vaudel, Marc Helgeland, Øyvind Falorni, Alberto Jørgensen, Anders Palmstrøm Hulting, Anna-Lena Svartberg, Johan Ekwall, Olov Fougner, Kristian Johan Wahlberg, Jeanette Nedrebø, Bjørn Gunnar Dahlqvist, Per Knappskog, Per Morten Wolff, Anette Susanne Bøe Bensing, Sophie Johansson, Stefan Kämpe, Olle Husebye, Eystein Sverre |
| author_facet | Eriksson, Daniel Røyrvik, Ellen Christine Aranda-Guillén, Maribel Berger, Amund Holte Landegren, Nils Artaza, Haydee Hallgren, Åsa Grytaas, Marianne Aardal Ström, Sara Bratland, Eirik Botusan, Ileana Ruxandra Oftedal, Bergithe Eikeland Breivik, Lars Vaudel, Marc Helgeland, Øyvind Falorni, Alberto Jørgensen, Anders Palmstrøm Hulting, Anna-Lena Svartberg, Johan Ekwall, Olov Fougner, Kristian Johan Wahlberg, Jeanette Nedrebø, Bjørn Gunnar Dahlqvist, Per Knappskog, Per Morten Wolff, Anette Susanne Bøe Bensing, Sophie Johansson, Stefan Kämpe, Olle Husebye, Eystein Sverre |
| author_sort | Eriksson, Daniel |
| collection | PubMed |
| description | Autoimmune Addison’s disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10(−8)). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7–4.3), P = 9.0 × 10(−25)) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35–41% of heritability (h(2)). |
| format | Online Article Text |
| id | pubmed-7878795 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-78787952021-02-24 GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility Eriksson, Daniel Røyrvik, Ellen Christine Aranda-Guillén, Maribel Berger, Amund Holte Landegren, Nils Artaza, Haydee Hallgren, Åsa Grytaas, Marianne Aardal Ström, Sara Bratland, Eirik Botusan, Ileana Ruxandra Oftedal, Bergithe Eikeland Breivik, Lars Vaudel, Marc Helgeland, Øyvind Falorni, Alberto Jørgensen, Anders Palmstrøm Hulting, Anna-Lena Svartberg, Johan Ekwall, Olov Fougner, Kristian Johan Wahlberg, Jeanette Nedrebø, Bjørn Gunnar Dahlqvist, Per Knappskog, Per Morten Wolff, Anette Susanne Bøe Bensing, Sophie Johansson, Stefan Kämpe, Olle Husebye, Eystein Sverre Nat Commun Article Autoimmune Addison’s disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10(−8)). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7–4.3), P = 9.0 × 10(−25)) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35–41% of heritability (h(2)). Nature Publishing Group UK 2021-02-11 /pmc/articles/PMC7878795/ /pubmed/33574239 http://dx.doi.org/10.1038/s41467-021-21015-8 Text en © The Author(s) 2021 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/. |
| spellingShingle | Article Eriksson, Daniel Røyrvik, Ellen Christine Aranda-Guillén, Maribel Berger, Amund Holte Landegren, Nils Artaza, Haydee Hallgren, Åsa Grytaas, Marianne Aardal Ström, Sara Bratland, Eirik Botusan, Ileana Ruxandra Oftedal, Bergithe Eikeland Breivik, Lars Vaudel, Marc Helgeland, Øyvind Falorni, Alberto Jørgensen, Anders Palmstrøm Hulting, Anna-Lena Svartberg, Johan Ekwall, Olov Fougner, Kristian Johan Wahlberg, Jeanette Nedrebø, Bjørn Gunnar Dahlqvist, Per Knappskog, Per Morten Wolff, Anette Susanne Bøe Bensing, Sophie Johansson, Stefan Kämpe, Olle Husebye, Eystein Sverre GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title | GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title_full | GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title_fullStr | GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title_full_unstemmed | GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title_short | GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility |
| title_sort | gwas for autoimmune addison’s disease identifies multiple risk loci and highlights aire in disease susceptibility |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878795/ https://www.ncbi.nlm.nih.gov/pubmed/33574239 http://dx.doi.org/10.1038/s41467-021-21015-8 |
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