Disentangling the comorbidity between allergic disease and type 1 diabetes using genetically informative designs.

Background: Previous research has demonstrated co-occurrence of asthma and type 1 diabetes in children, but the relationship is not as clear between allergic rhinitis or eczema and type 1 diabetes. Shared familial factors could explain a comorbidity, but the genetic overlap remains to be examined. Objective: The aim was to further the etiologic understanding of the comorbidity between allergic disease and type 1 diabetes. Methods: A Swedish population-based cohort of 3 million children born 1987-2017 was linked to nationwide registers. Associations between each allergic disease and type 1 diabetes were estimated within individuals and the familial coaggregation between relatives. For the genetic overlap, linkage disequilibrium score regression was applied on the basis of genome-wide association studies. In genotyped individuals from the Swedish Twin Registry, polygenic risk scores were developed to test the prediction of genetic risk of one disease on the phenotype of the other. Results: Asthma, allergic rhinitis, and eczema were associated with type 1 diabetes (odds ratio [95% confidence interval], 1.11 [1.07-1.15] for asthma, 1.23 [1.19-1.27] for allergic rhinitis, and 1.31 [1.26-1.35] for eczema). Familial coaggregation was only detected for asthma or allergic rhinitis, not for eczema. Linkage disequilibrium score regression and polygenic risk score analysis yielded little evidence for a genetic overlap. Conclusions: Allergic diseases and type 1 diabetes seem to co-occur in individuals. For asthma and allergic rhinitis, this association existed also between relatives indicating a shared etiology but was not evident for eczema. No strong signals of a genetic overlap using molecular genetic approaches were uncovered.