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Genetic variation affecting absorption, distribution or excretion of essential trace elements may lead to health effects related to sub-clinical deficiency. We have tested for allelic effects of single-nucleotide polymorphisms (SNPs) on blood copper, selenium and zinc in a genome-wide association study using two adult cohorts from Australia and the UK. Participants were recruited in Australia from twins and their families and in the UK from pregnant women. We measured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasma mass spectrometry. Genotyping was performed with Illumina chips and &gt;2.5 m SNPs were imputed from HapMap data. Genome-wide significant associations were found for each element. For Cu, there were two loci on chromosome 1 (most significant SNPs rs1175550,  P  = 5.03 × 10 −10 , and rs2769264,  P  = 2.63 × 10 −20 ); for Se, a locus on chromosome 5 was significant in both cohorts (combined  P  = 9.40 × 10 −28  at rs921943); and for Zn three loci on chromosomes 8, 15 and X showed significant results (rs1532423,  P  = 6.40 × 10 −12 ; rs2120019,  P  = 1.55 × 10 −18 ; and rs4826508,  P  = 1.40 × 10 −12 , respectively). The Se locus covers three genes involved in metabolism of sulphur-containing amino acids and potentially of the analogous Se compounds; the chromosome 8 locus for Zn contains multiple genes for the Zn-containing enzyme carbonic anhydrase. Where potentially relevant genes were identified, they relate to metabolism of the element (Se) or to the presence at high concentration of a metal-containing protein (Cu).

Genome-wide association study identifies loci affecting blood copper, selenium and zinc