GWAS for autoimmune Addison's disease identifies multiple risk loci and highlights AIRE in disease susceptibility.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 33574239.
- Also identified by DOI 10.1038/s41467-021-21015-8 and PMC identifier 7878795.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-8</sup>). 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<sup>-25</sup>) 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<sup>2</sup>).
Medical subject headings
- Addison Disease
- Genome-Wide Association Study