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

Borné, Yan LU ; Söderholm, Martin LU ; Barregard, Lars; Fagerberg, Björn; Persson, Margaretha LU ; Melander, Olle LU ; Thévenod, Frank; Hedblad, Bo LU and Engström, Gunnar LU (2016) In Human Molecular Genetics 25(11). p.2342-2348
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
25
issue
11
pages
2342 - 2348
publisher
Oxford University Press
external identifiers
  • scopus:84998538610
ISSN
0964-6906
DOI
10.1093/hmg/ddw083
language
English
LU publication?
yes
id
3b794396-5a4c-4ad5-b179-2dfdff10478b
date added to LUP
2016-04-12 13:20:10
date last changed
2017-01-15 04:37:55
@article{3b794396-5a4c-4ad5-b179-2dfdff10478b,
  abstract     = {<p>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.</p><p>OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes.</p><p>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.</p><p>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.</p><p>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.</p>},
  author       = {Borné, Yan and Söderholm, Martin and Barregard, Lars and Fagerberg, Björn and Persson, Margaretha and Melander, Olle and Thévenod, Frank and Hedblad, Bo and Engström, Gunnar},
  issn         = {0964-6906},
  language     = {eng},
  month        = {06},
  number       = {11},
  pages        = {2342--2348},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Genome wide association study identifies two loci associated with cadmium in erythrocytes among never-smokers},
  url          = {http://dx.doi.org/10.1093/hmg/ddw083},
  volume       = {25},
  year         = {2016},
}