Metal elements are present in the human body, and their levels in the blood have important impacts on health. In this study, 2488 Chinese individuals were included in a genome-wide association study of 21 serum metal levels, with approximately 179,000 East Asian individuals in a bidirectional two-sample Mendelian randomization (MR) analysis, and 628,000 Europeans in a two-sample MR analysis. We identified two single nucleotide polymorphisms (SNPs) rs35691438 and rs671 that were significantly associated with serum copper levels (SCLs). The bidirectional two-sample MR analysis in the East Asian population showed that gamma-glutamyl transpeptidase levels have a causal effect on SCLs. SCLs have causal effects on six outcomes, namely risks of esophageal varix, glaucoma, sleep apnea syndrome, and systemic lupus erythematosus, white blood cell count, and usage of drugs affecting bone structure and mineralization. The two-sample MR analyses in the European population showed causal effects of erythrocyte copper levels on risks of carpal tunnel syndrome and compression fracture. Our results provide original insights into the causal relationship between blood metal levels and multiple human phenotypes.
© 2022. The Author(s).