The UK Biobank (UKBB) is a large population-based cohort that provides a unique opportunity to study the association between environmental exposure and biomarkers and to identify biomarkers as potential instruments for assessing exposure dose, health damage, and disease risks. On 462 063 participants of European ancestry, we characterized the relationship of 38 disease-relevant biomarkers, asthma diagnosis, ambient pollution, traffic factors, and genetic background. The air pollutant exposure on the UKBB cohort was fairly low (e.g., mean PM2.5 concentration at 10.0 μg/m3). Nevertheless, 30 biomarkers were in association with at least one environmental factor; e.g., C-reactive protein levels were positively associated with NO (p adj = 2.99 × 10–4), NO2 (p adj = 4.15 × 10–4), and PM2.5 (p adj = 1.92 × 10–6) even after multiple testing adjustment. Asthma diagnosis was associated with four pollutants (NO, NO2, PM2.5, and PM10). The largest effect size was observed in PM2.5, where a 5 μg/m3 increment of exposure was associated with a 1.52 increase in asthma diagnosis (p = 4.41 × 10–13). Further, environmental exposure and genetic predisposition influenced biomarker levels and asthma diagnosis in an additive model. The exposure–biomarker associations identified in this study could serve as potential indicators for environmental exposure induced health damages. Our results also shed light on possible mechanisms whereby environmental exposure influences disease-causing biomarkers and in turn increases disease risk.

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