Abstract

Background: Sarcoidosis is a multiorgan, granulomatous, inflammatory disease with unknown aetiology. Familial clustering of cases and ethnic variation in the epidemiology suggests a genetic influence on the disease susceptibility.

Aim: This paper reports twin concordance and heritability estimates of sarcoidosis in order to assess the overall contribution of genetic factors to the disease susceptibility.

Methods: Monozygotic and dizygotic twins enrolled in either the Danish or the Finnish population-based, national Twin Cohorts (61,662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland, registry of re-imbursed medication using the 8th and 10th editions of the International Classification of Diseases. Fisher's exact test was used to compare probandwise concordance rates in different zygosity groups. Heritability was estimated based on a multifactorial threshold liability model.

Results: A total of 210 twin pairs with at least one proband with a diagnosis of sarcoidosis were identified. The probandwise concordance rate was higher in monozygotic than in dizygotic twins, 0.148 vs. 0.012. Compared to the general population we found an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was on the other hand only 7-fold. Aetiological model fitting gave a heritability of sarcoidosis of 0.66 (95% CI 0.45-0.80).

Conclusions: This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis. This result should encourage the search for molecular genetic markers of the susceptibility to disease.