Familial Coaggregation of Asthma and Type 1 Diabetes in Children

Abstract

Importance: The association between atopic and autoimmune disease, particularly asthma and type 1 diabetes, has been debated. Further understanding of the underlying factors associated with the comorbidity in children is warranted.

Objectives: To assess the bidirectional association between asthma and type 1 diabetes and examine the possibility of a shared risk for the diseases by studying their pattern of familial coaggregation.

Design, setting, and participants: A birth cohort study of children born from January 1, 2001, and followed up until December 31, 2015, was performed. Population data were obtained from multiple national Swedish registers. A total of 1 347 901 singleton children, live-born in Sweden between January 1, 2001, and December 31, 2013, were identified, and children with incomplete data were excluded. The remaining 1 284 748 children were linked to their biological full siblings, maternal and paternal half-siblings, cousins, and half-cousins. Data analysis was conducted from April 1, 2019, to January 17, 2020.

Main outcomes and measures: Cases of asthma and type 1 diabetes were defined using a combination of diagnoses and medication prescriptions found in the registers.

Results: In the cohort of 1 284 748 children, 660 738 children (51.4%) were boys; 121 809 children (9.5%) had asthma, 3812 children (0.3%) had type 1 diabetes, and 494 children had both asthma and type 1 diabetes, representing 0.4% of all asthma or 13% of all type 1 diabetes. Mean (SD) age at diagnosis was 3.0 (2.8) years for children with asthma, and 5.9 (3.3) years for those with type 1 diabetes. Asthma and type 1 diabetes were associated within individuals (odds ratio, 1.15; 95% CI, 1.05-1.27). Children with asthma had an increased risk of subsequent type 1 diabetes (hazard ratio, 1.16; 95% CI, 1.06-1.27); however, subsequent asthma risk did not differ substantially among children with type 1 diabetes (hazard ratio, 0.92; 95% CI, 0.75-1.12). Siblings of individuals with asthma were at an increased risk of type 1 diabetes (odds ratio, 1.27; 95% CI, 1.13-1.42) and vice versa. The results remained positive after controlling for the direct association of one disease with the other.

Conclusions and relevance: This study appears to provide evidence for co-occurrence, importance of sequential appearance, and coaggregation of asthma and type 1 diabetes in children and their siblings. The findings may suggest shared familial factors contributing to the associations. Knowledge of the nature of the association could be of importance in future clinical practice.

Figure 1.. Description of the Study Population

Children born in Sweden between January 1, 2001, and December 31, 2013, were identified from the Medical Birth Register. Only live-born, singleton children were included, and children with missing data from various Swedish national registers were excluded.

Figure 2.. Familial Coaggregation of Asthma and Type 1 Diabetes

Crude odds ratios (ORs) represent the bidirectional association between asthma and type 1 diabetes across different types of relatives, and actual values are displayed on a logarithmic scale. Full data for familial coaggregation analyses are found in eTable 2 in the Supplement.