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

Abstract

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 > 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).

Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis

“…Currently, there is no internationally acceptable value or range for plasma selenium concentration in the general population. Thus, it remains to be elucidated whether or to what extent the discrepancies regarding plasma selenium concentrations could be explained by its exposure levels, effects of genetic predisposition and other predisposing factors on its metabolism39, between-laboratory differences in methods (ICP-MS vselectrothermal atomic absorption spectrometry) and measurement errors, or variations in population characteristics among studies.…”

“…For the general population, the primary exposure pathways, in order of decreasing relative proportions, are food, water, and air39. Some studies found high amounts of selenium in foods like nuts, seafood, meats and wheat40.…”

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women

“…Differences in trace element concentration could result from soil, geographical location, food preparation and processing, food accessibility, cultural practices, pollution, or ethnic differences in body composition and genetics [7]. A recent genome-wide association study has identified loci affecting blood Cu, Se, and Zn from 2603 Australian and 2874 British participants [4]. …”

“…Nutrient status, including the bioavailability and concentration of trace elements, is known to be influenced by many physiological and diet factors, such as soil, geographical location, food preparation, pollution, body composition, and ethnicity [4,5,6]. During pregnancy, both physiological variables and diet influence the availability of trace elements for digestion, absorption, and utilization [7].…”

Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study

“…Individuals with incorrect sex assignments, unusual genome-wide or X-chromosome heterozygosity, disproportionate levels of individual missingness (>5%), evidence of cryptic relatedness (>12.5% identity-by-descent [IBD]), or those of non-European ancestry determined from multidimensional scaling analysis seeded with individuals from the International HapMap project [29] were excluded. The resulting dataset consisted of 8340 individuals [30]. …”