Non-genetic and genetic determinants of serum selenium and selenium species in the Aragon Workers Health Study

Understanding potential determinants of selenium biomarkers can help to unravel selenium health effects. We evaluated the contribution of non-genetic (sociodemographic and lifestyle) and genetic factors to serum selenium biomarkers and selenium species (quantified as selenium) including selenium in glutathione peroxidase (GPx), selenoprotein P (SeP), selenoalbumin (SeAlb) and total selenometabolites (Se-metabolites) in the Aragon Workers Health Study (AWHS), a predominantly male cohort of car assembly factory workers in Spain. Total serum selenium and selenium species were measured by HPLC/ICP-QQQ-MS in 1624 AWHS participants. Blood and urine selenium, measured by ICP-MS, were available in a subset. A Healthy Lifestyle Score (HLS) included Mediterranean diet, physical activity, smoking, BMI and alcohol intake. Candidate gene and genome-wide discovery analyses (CGA and GDA, respectively) were based on TOPMed imputed SNPs. In sex and age-adjusted models, overall HLS, physical activity, and specific foods intake showed positive associations with serum total selenium, SeAlb and Se-metabolites concentrations. The associations between smoking status and BMI with total serum selenium; age, smoking status, BMI and meat intake with SeAlb; and smoking status with Se-metabolites, were inverse. In the GDA, we identified 20, 24, 21, 26, 16, 20 and 68 independent genetic loci for serum total selenium, GPx, SeP, SeAlb, Se-metabolites, and total blood and urine selenium, respectively, with some overlapping genes also relevant in the CGA. Enrichment analysis pointed to biological pathways including circadian rhythm regulation, immune system processes, signaling and receptor- and transporter-related pathways. The explained variability of selenium markers ranged from 15 % for SeP to 21 % for SeAlb and from 0.2 % for SeP to 3.5 % for SeAlb in environmental determinants-adjusted models with and without the specific selenium biomarker polygenic score, respectively. While the genetic contribution is substantial, selenium status might be influenced by reinforced healthy lifestyle interventions. Follow-up genetic studies to evaluate selenium health consequences are granted.