OR19-1 Heritability and Etiological Overlap in Seven Autoimmune Diseases: A Population-Based Swedish Twin Study

With few exceptions, autoimmune diseases (AIDs) are genetically complex disorders. Familial aggregation of AIDs is common, and it is therefore not surprising that many genetic risk markers in autoimmunity are pleiotropic (1). Despite this, etiologic overlap across AIDs has not yet been explored in an unbiased fashion. We therefore used the Swedish Twin Registry to study heritability and overlap between seven AIDs known to cluster. Using data on 116,320 twins of known zygosity, we identified 1,957 subjects with a diagnosis of Hashimoto’s thyroiditis, 762 with atrophic gastritis, 723 with celiac disease, 645 with Grave’s disease, 420 with type-1 diabetes, 192 with vitiligo and 31 with autoimmune Addison’s disease. Heritability for individual disorders ranged from 0.97 for Addison´s disease to 0.47 for pernicious anemia using AE-models (additive genetic and unique environmental effects). Probandwise concordance rates ranged from 0.71 in monozygotic twins (MZ) with Addison’s disease to 0 in dizygotic twins (DZ) with Addison’s disease and vitiligo. Rates were higher in MZ than in DZ pairs for all seven diseases. Probandwise pseudo-concordance was defined as the proportion of co-twins with a different AID among twins with index AID. Total probandwise concordance was defined as the proportion of co-twins with (any of the studied) AIDs among twins with index AID. The ratio of probandwise pseudo-concordance to total probandwise concordance was used as a measure of autoimmune clustering. This ratio was highest for Addison’s disease (MZ 0.54, DZ 1.0) and vitiligo (MZ 0.46, DZ 1.0), lower for Hashimoto’s thyroiditis (MZ 0.29, DZ 0.29) and lowest for Celiac disease (MZ 0.12, DZ 0.31). In the context of the seven AIDs explored here, probandwise concordance rates for individual diseases underestimate the burden of autoimmunity. This effect is considerable for disorders with significant etiological overlap, such as Addison’s disease and vitiligo, but marginal in celiac disease, which has little etiological overlap. The genetic influence on disease occurrence for individual disorders is high, with heritability estimates ranging from 0.97 to 0.47. 1. Cotsapas C, Voight BF, Rossin E, et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet 2011;7(8):e1002254. doi: 10.1371/journal.pgen.1002254