Childhood type 1 diabetes: an environment-wide association study across England

AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disease affecting ~400,000 people across the UK. It is likely that environmental factors trigger the disease process in genetically susceptible individuals. We assessed the associations between a wide range of environmental factors and childhood type 1 diabetes incidence in England, using an agnostic, ecological environment-wide association study (EnWAS) approach, to generate hypotheses about environmental triggers. METHODS: We undertook analyses at the local authority district (LAD) level using a national hospital episode statistics-based incident type 1 diabetes dataset comprising 13,948 individuals with diabetes aged 0–9 years over the period April 2000 to March 2011. We compiled LAD level estimates for a range of potential demographic and environmental risk factors including meteorological, land use and environmental pollution variables. The associations between type 1 diabetes incidence and risk factors were assessed via Poisson regression, disease mapping and ecological regression. RESULTS: Case counts by LAD varied from 1 to 236 (median 33, interquartile range 24–46). Overall type 1 diabetes incidence was 21.2 (95% CI 20.9, 21.6) per 100,000 individuals. The EnWAS and disease mapping indicated that 15 out of 53 demographic and environmental risk factors were significantly associated with diabetes incidence, after adjusting for multiple testing. These included air pollutants (particulate matter, nitrogen dioxide, nitrogen oxides, carbon monoxide; all inversely associated), as well as lead in soil, radon, outdoor light at night, overcrowding, population density and ethnicity. Disease mapping revealed spatial heterogeneity in type 1 diabetes risk. The ecological regression found an association between type 1 diabetes and the living environment domain of the Index of Multiple Deprivation (RR 0.995; 95% credible interval [CrI] 0.991, 0.998) and radon potential class (RR 1.044; 95% CrI 1.015, 1.074). CONCLUSIONS/INTERPRETATION: Our analysis identifies a range of demographic and environmental factors associated with type 1 diabetes in children in England. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05087-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.