GWAS for autoimmune Addison's disease identifies multiple risk loci and highlights AIRE in disease susceptibility.
Nat Commun
; 12(1): 959, 2021 02 11.
Article
de En
| MEDLINE
| ID: mdl-33574239
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).
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie d'Addison
/
Étude d'association pangénomique
Type d'étude:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Female
/
Humans
/
Male
Langue:
En
Journal:
Nat Commun
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
Suède