Format

Send to

Choose Destination
Endocrine. 2017 Dec;58(3):521-527. doi: 10.1007/s12020-017-1441-z. Epub 2017 Oct 16.

Heritability of Addison's disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins.

Author information

1
Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden. jakob.skov@liv.se.
2
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
3
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
4
Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
5
Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden.

Abstract

PURPOSE:

The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins.

METHODS:

A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies.

RESULTS:

We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs.

CONCLUSIONS:

The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.

KEYWORDS:

Addison’s disease; Autoimmunity; Heritability; Polyglandular; Registries; Twins

PMID:
29039147
PMCID:
PMC5693969
DOI:
10.1007/s12020-017-1441-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center