Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population.

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10). ADAMTSL1 rs17229526 (p = 4.96 × 10) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.