The genetics of autoimmune Addison disease: past, present an
Autoimmune Addison disease is an endocrinopathy that is fatal if not diagnosed and treated in a timely manner. Its rarity has hampered unbiased studies of the predisposing genetic factors. A 2021 genome-wide association study, explaining up to 40% of the genetic susceptibility, has revealed new disease loci and reproduced some of the previously reported associations, while failing to reproduce others. Credible risk loci from both candidate gene and genome-wide studies indicate that, like one of its most common comorbidities, type 1 diabetes mellitus, Addison disease is primarily caused by aberrant T cell behavior. Here, we review the current understanding of the genetics of autoimmune Addison disease and its position in the wider field of autoimmune disorders. The mechanisms that could underlie the effects on the adrenal cortex are also discussed.

Autoimmune Addison disease (AAD) is an oligogenic complex disease.
Genetic risk loci for AAD largely overlap with known autoimmune comorbidities.
In particular, HLA and autoimmune regulator (AIRE) variants predispose to AAD.
Probable functional elements of genetic risk variants highlight a T cell etiology for AAD.