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Rare copy number variation in autoimmune Addison's disease.
Artaza, Haydee; Eriksson, Daniel; Lavrichenko, Ksenia; Aranda-Guillén, Maribel; Bratland, Eirik; Vaudel, Marc; Knappskog, Per; Husebye, Eystein S; Bensing, Sophie; Wolff, Anette S B; Kämpe, Olle; Røyrvik, Ellen C; Johansson, Stefan.
Afiliação
  • Artaza H; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Eriksson D; K. G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.
  • Lavrichenko K; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Aranda-Guillén M; Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
  • Bratland E; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Vaudel M; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Knappskog P; Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
  • Husebye ES; K. G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.
  • Bensing S; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
  • Wolff ASB; Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Kämpe O; Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Røyrvik EC; Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
  • Johansson S; Department of Genetics and Bioinformatics, Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
Front Immunol ; 15: 1374499, 2024.
Article em En | MEDLINE | ID: mdl-38562931
ABSTRACT
Autoimmune Addison's disease (AAD) is a rare but life-threatening endocrine disorder caused by an autoimmune destruction of the adrenal cortex. A previous genome-wide association study (GWAS) has shown that common variants near immune-related genes, which mostly encode proteins participating in the immune response, affect the risk of developing this condition. However, little is known about the contribution of copy number variations (CNVs) to AAD susceptibility. We used the genome-wide genotyping data from Norwegian and Swedish individuals (1,182 cases and 3,810 controls) to investigate the putative role of CNVs in the AAD aetiology. Although the frequency of rare CNVs was similar between cases and controls, we observed that larger deletions (>1,000 kb) were more common among patients (OR = 4.23, 95% CI 1.85-9.66, p = 0.0002). Despite this, none of the large case-deletions were conclusively pathogenic, and the clinical presentation and an AAD-polygenic risk score were similar between cases with and without the large CNVs. Among deletions exclusive to individuals with AAD, we highlight two ultra-rare deletions in the genes LRBA and BCL2L11, which we speculate might have contributed to the polygenic risk in these carriers. In conclusion, rare CNVs do not appear to be a major cause of AAD but further studies are needed to ascertain the potential contribution of rare deletions to the polygenic load of AAD susceptibility.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Addison Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Addison Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article