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

Journal article
Authors Y. Borne
M. Soderholm
Lars Barregård
Björn Fagerberg
M. Persson
O. Melander
F. Thevenod
B. Hedblad
G. Engstrom
Published in Hum Mol Genet
Volume 25
Issue 11
Pages 2342-2348
ISSN 0964-6906
Publication year 2016
Published at Institute of Medicine, School of Public Health and Community Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 2342-2348
Language en
Keywords obsessive-compulsive disorder, food frequency questionnaire, diet, history method, cardiovascular-disease, prospective cohort, malmo food, exposure, blood, lead, population, Biochemistry & Molecular Biology, Genetics & Heredity
Subject categories Clinical Medicine


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 Malmo 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, 14 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 the XKR9 and LACTB2 genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, minor allele frequency [MAF] = 0.46, beta: -0.11, P = 3.48 x 10(-11)), an intron variant within the XKR9 gene. The other significant locus, rs17574271 (minor allele C, MAF = 0.09, beta: 0.17, P = 6.18 x 10(-9)), was an intron variant within the DLGAP1 gene 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 the XKR9 and LACTB2 genes, 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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