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 of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find 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 current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

微量元素对人类健康很重要，但可能产生毒性或不利影响。摄取、分布、代谢和排泄的机制部分受到遗传控制，但尚未得到广泛的绘制。在此，我们报告了一项针对 57 种必需和非必需微量元素的全面多元素全基因组关联研究。我们对多达 6564 个斯堪的纳维亚全血样本中的 14 种微量元素进行全基因组关联荟萃分析，并对仅在特伦德拉健康研究 (HUNT) 中测量的多达 2819 个样本中的 43 种微量元素进行全基因组关联研究。我们在全基因组关联荟萃分析中确定了 11 个与砷、镉、锰、硒和锌血液浓度相关的新基因位点。在 HUNT 中，还指出了其他微量元素的几个全基因组重要位点。使用两个样本孟德尔随机化，我们发现了对健康结果有弱到中度影响的几种迹象，最精确的是增加锌对前列腺癌的弱有害影响。然而，需要独立验证。我们目前对微量元素相关遗传变异的了解可能有助于确定微量元素对人类健康的影响。