TY - JOUR
T1 - Genome-wide association study identifies loci affecting blood copper, selenium and zinc
AU - Evans, David M.
AU - Zhu, Gu
AU - Dy, Veronica
AU - Heath, Andrew C.
AU - Madden, Pamela A.F.
AU - Kemp, John P.
AU - McMahon, George
AU - Pourcain, Beate St
AU - Timpson, Nicholas J.
AU - Golding, Jean
AU - Lawlor, Debbie A.
AU - Steer, Colin
AU - Montgomery, Grant W.
AU - Martin, Nicholas G.
AU - Smith, George Davey
AU - Whitfield, John B.
N1 - Funding Information:
Sample collection, and the recruitment and interviewing of participants, was funded by grants AA007535, AA013320, AA013321, AA013326 and DA012854 from the US National Institutes of Health to A.C.H., N.G.M., P.A.F.M., and the late Richard Todd, MD, PhD. Biomarker measurement was supported by AA014041 to J.B.W. G.W.M. is supported by the National Health and Medical Research Council of Australia Fellowship Scheme. The UK Medical Research Council, the Wellcome Trust (grant ref: 092731), and the University of Bristol currently provide core support for the Avon Longitudinal Study of Parents and their Children. J.P.K. was funded by a Wellcome Trust 4-year PhD studentship in molecular, genetic, and life course epidemiology (WT083431MA).
PY - 2013/10
Y1 - 2013/10
N2 - 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.Wemeasured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasmamass spectrometry. Genotyping was performed with Illumina chips and >2.5 m SNPs were imputed fromHapMap 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 5 9.40 3 10228 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 Selocus 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 ametal-containing protein (Cu).
AB - 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.Wemeasured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasmamass spectrometry. Genotyping was performed with Illumina chips and >2.5 m SNPs were imputed fromHapMap 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 5 9.40 3 10228 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 Selocus 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 ametal-containing protein (Cu).
UR - http://www.scopus.com/inward/record.url?scp=84881530978&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddt239
DO - 10.1093/hmg/ddt239
M3 - Article
C2 - 23720494
AN - SCOPUS:84881530978
SN - 0964-6906
VL - 22
SP - 3998
EP - 4006
JO - Human molecular genetics
JF - Human molecular genetics
IS - 19
ER -