Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden

Sci Rep. 2018 May 30;8(1):8395. doi: 10.1038/s41598-018-26842-2.

Abstract

Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / genetics*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • CTLA-4 Antigen / genetics
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Genomics
  • Haplotypes
  • Humans
  • Lectins, C-Type / genetics
  • Monosaccharide Transport Proteins / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Sweden
  • Transcription Factors / genetics*

Substances

  • APECED protein
  • BACH2 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • CLEC16A protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • Transcription Factors
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22