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Genome-wide association study of toxic metals and trace elements reveals novel associations
Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala Univ, Dept Med Sci Occupat & Environm Med, S-75185 Uppsala, Sweden..ORCID-id: 0000-0002-8949-3555
Harvard Univ, Inst Technol, Broad Inst Massachusetts, Cambridge, MA 02142 USA..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0003-2256-6972
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2015 (engelsk)Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 16, s. 4739-4745Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The accumulation of toxic metals in the human body is influenced by exposure and mechanisms involved in metabolism, some of which may be under genetic control. This is the first genome-wide association study to investigate variants associated with whole blood levels of a range of toxic metals. Eleven toxic metals and trace elements (aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead and zinc) were assayed in a cohort of 949 individuals using mass spectrometry. DNA samples were genotyped on the Infinium Omni Express bead microarray and imputed up to reference panels from the 1000 Genomes Project. Analyses revealed two regions associated with manganese level at genome-wide significance, mapping to 4q24 and 1q41. The lead single nucleotide polymorphism(SNP) in the 4q24 locus was rs13107325 (P-value = 5.1 x 10(-11), beta = -0.77), located in an exon of SLC39A8, which encodes a protein involved in manganese and zinc transport. The lead SNP in the 1q41 locus is rs1776029 (P-value = 2.2 x 10(-14), beta = -0.46). The SNP lies within the intronic region of SLC30A10, another transporter protein. Among other metals, the loci 6q14.1 and 3q26.32 were associated with cadmium and mercury levels (P = 1.4x10(-10), beta = -1.2 and P = 1.8x10(-9), beta = -1.8, respectively). Whole blood measurements of toxicmetals are associated with genetic variants in metal transporter genes and others. This is relevant in inferring metabolic pathways of metals and identifying subsets of individuals who may be more susceptible to metal toxicity.

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2015. Vol. 24, nr 16, s. 4739-4745
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URN: urn:nbn:se:uu:diva-264674DOI: 10.1093/hmg/ddv190ISI: 000361315400021PubMedID: 26025379OAI: oai:DiVA.org:uu-264674DiVA, id: diva2:861313
Forskningsfinansiär
Wellcome trust, WT098017 WT090532 097306/Z/11/Z WT064890Tilgjengelig fra: 2015-10-16 Laget: 2015-10-15 Sist oppdatert: 2018-01-11bibliografisk kontrollert

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