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

Journal article
Authors J. Skov
D. Eriksson
R. Kuja-Halkola
J. Hoijer
Soffia Gudbjörnsdottir
Ann-Marie Svensson
P. K. E. Magnusson
J. F. Ludvigsson
O. Kampe
S. Bensing
Published in European Journal of Endocrinology
Volume 182
Issue 5
Pages 473-480
ISSN 0804-4643
Publication year 2020
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 473-480
Language en
Links dx.doi.org/10.1530/eje-20-0049
Keywords celiac-disease, genetics, comorbidities, epidemiology, metaanalysis, concordance, prevalence, nationwide, vitiligo, age, Endocrinology & Metabolism
Subject categories Internal medicine

Abstract

Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co- aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate 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 tha n 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 r esults validate and refine previous heritability estimates based on smaller twin cohorts.

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