| Literature DB >> 33574239 |
Daniel Eriksson1,2,3, Ellen Christine Røyrvik4,5, Maribel Aranda-Guillén1, Amund Holte Berger4,5,6, Nils Landegren1,7, Haydee Artaza4,5, Åsa Hallgren1, Marianne Aardal Grytaas4,8, Sara Ström9,10, Eirik Bratland4,5,6, Ileana Ruxandra Botusan9,10, Bergithe Eikeland Oftedal4,5, Lars Breivik4,8, Marc Vaudel11, Øyvind Helgeland11,12, Alberto Falorni13, Anders Palmstrøm Jørgensen14, Anna-Lena Hulting10, Johan Svartberg15,16, Olov Ekwall17,18, Kristian Johan Fougner19, Jeanette Wahlberg20,21, Bjørn Gunnar Nedrebø4,22, Per Dahlqvist23, Per Morten Knappskog4,5,6, Anette Susanne Bøe Wolff4,5, Sophie Bensing9,10, Stefan Johansson4,6, Olle Kämpe24,25,26,27, Eystein Sverre Husebye28,29,30,31.
Abstract
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 (h2).Entities:
Year: 2021 PMID： 33574239 DOI： 10.1038/s41467-021-21015-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919