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. 2020 May;182(5):473-480.
doi: 10.1530/EJE-20-0049.

Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study

Jakob Skov  1   2 , Daniel Eriksson  3   4 , Ralf Kuja-Halkola  5 , Jonas Höijer  6 , Soffia Gudbjörnsdottir  7   8 , Ann-Marie Svensson  8 , Patrik K E Magnusson  5 , Jonas F Ludvigsson  5   9 , Olle Kämpe  3   4   10 , Sophie Bensing  1   4
Affiliations

Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study

Jakob Skov et al. Eur J Endocrinol. 2020 May.

Abstract

Objective: Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environmental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organ-specific autoimmune diseases.

Design: Prospective twin cohort study.

Methods: We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data.

Results: Co-aggregation was more pronounced in monozygotic twins (median HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0.71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease.

Conclusions: Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.

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Figures

Figure 1
Figure 1
Familial aggregation and co-aggregation of autoimmunity. Hazard ratios for developing the same disease as present in the co-twin, a different disease, or any of the studied diseases. Monozygotic twins in black and dizygotic twins in red. *Any of the studied diseases.
See this image and copyright information in PMC

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