New insights into the genetic etiology of 57 essential and non-essential trace elements in humans

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study (GWAS) of 57 essential and non-essential trace elements. We performed GWA meta-analyses of 14 trace elements in up to 6580 Scandinavian whole-blood samples, and GWASs of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identified 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide meta-analyses. In HUNT, several genome-wide significant loci were also indicated for other trace elements. Using two-sample Mendelian randomization, we found several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our new understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.