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.

中文翻译：

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儿童 1 型糖尿病：英格兰的一项全环境关联研究。

目标/假设 1 型糖尿病是一种自身免疫性疾病，在英国影响约 400,000 人。环境因素很可能触发遗传易感个体的疾病过程。我们使用不可知论的全生态环境关联研究 (EnWAS) 方法评估了广泛的环境因素与英格兰儿童 1 型糖尿病发病率之间的关联，以生成有关环境触发因素的假设。方法 我们使用基于国家医院事件统计的 1 型糖尿病事件数据集在地方当局区 (LAD) 级别进行分析，该数据集包括 2000 年 4 月至 2011 年 3 月期间 13,948 名 0-9 岁糖尿病患者。我们编制了 LAD 级别估计值对于一系列潜在的人口和环境风险因素，包括气象、土地利用和环境污染变量。通过泊松回归、疾病图谱和生态回归评估 1 型糖尿病发病率与危险因素之间的关联。结果 LAD 的病例数从 1 到 236（中位数 33，四分位距 24-46）不等。1 型糖尿病的总体发病率为每 100,000 人 21.2 (95% CI 20.9, 21.6)。EnWAS 和疾病图谱表明，经过多次测试调整后，53 个人口和环境风险因素中有 15 个与糖尿病发病率显着相关。这些包括空气污染物（颗粒物、二氧化氮、氮氧化物、一氧化碳；所有这些都呈负相关），以及土壤中的铅、氡、夜间室外光、过度拥挤、人口密度和种族。疾病映射揭示了 1 型糖尿病风险的空间异质性。生态回归发现 1 型糖尿病与多重剥夺指数 (RR 0.995; 95% 可信区间 [CrI] 0.991, 0.998) 和氡潜在等级 (RR 1.044; 95% CrI 1.015, 1.074) 的生活环境领域之间存在关联）。结论/解释 我们的分析确定了一系列与英格兰儿童 1 型糖尿病相关的人口统计学和环境因素。