Genome wide association study identifies two loci associated with cadmium in erythrocytes among never-smokers

BACKGROUND: Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium.OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes.METHODS: Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmö Diet and Cancer cohort. Genotyping was performed using the Illumina HumanOmniExpressExome Bead chip with genome-wide coverage. Genome wide analyses were performed in the whole sample and in never smokers.RESULTS: No single nucleotide polymorphism (SNP) reached a genome-wide significant association with erythrocyte cadmium in the whole sample. However, in never smokers, fourteen variants showed genome-wide significant relationships with erythrocyte cadmium after adjusting for age and sex. Thirteen variants were in linkage disequilibrium on chromosome 8q13.3 in theXKR9andLACTB2genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, MAF=0.46, β: -0.11, p=3.48 x 10(-11)), an intron variant within theXKR9gene. The other significant locus, rs17574271 (minor allele C, MAF=0.09, β: 0.17, p=6.18 x 10(-9)), was an intron variant within theDLGAP1gene at chromosome 18p11.31.CONCLUSION: This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers theXKR9andLACTB2genes, which both could have related functions in cadmium absorption and metabolism. Replication studies are needed to confirm the findings and mechanisms should be further investigated