Genome-wide association study identifies genetic loci associated with iron deficiency

Christine E. McLaren, Chad P. Garner, Clare C. Constantine, Stela McLachlan, Chris D. Vulpe, Beverly M. Snively, Victor R. Gordeuk, Debbie A. Nickerson, James D. Cook, Catherine Leiendecker-Foster, Kenneth B. Beckman, John H. Eckfeldt, Lisa F. Barcellos, Joseph A Murray, Paul C. Adams, Ronald T. Acton, Anthony A. Killeen, Gordon D. McLaren

Research output: Contribution to journalArticle

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Abstract

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 μg/L (cases) and iron replete controls (SF>100 μg/L in men, SF>50 μg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10-7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10-9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification.

Original languageEnglish (US)
Article numbere17390
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - 2011

Fingerprint

Genetic Loci
Genome-Wide Association Study
Iron
Genes
iron
veterans
loci
Single Nucleotide Polymorphism
Veterans
Transferrin
Ferritins
ferritin
Polymorphism
transferrin
hemochromatosis
single nucleotide polymorphism
Iron Overload
Hemochromatosis
iron overload
Serum

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

McLaren, C. E., Garner, C. P., Constantine, C. C., McLachlan, S., Vulpe, C. D., Snively, B. M., ... McLaren, G. D. (2011). Genome-wide association study identifies genetic loci associated with iron deficiency. PLoS One, 6(3), [e17390]. https://doi.org/10.1371/journal.pone.0017390

Genome-wide association study identifies genetic loci associated with iron deficiency. / McLaren, Christine E.; Garner, Chad P.; Constantine, Clare C.; McLachlan, Stela; Vulpe, Chris D.; Snively, Beverly M.; Gordeuk, Victor R.; Nickerson, Debbie A.; Cook, James D.; Leiendecker-Foster, Catherine; Beckman, Kenneth B.; Eckfeldt, John H.; Barcellos, Lisa F.; Murray, Joseph A; Adams, Paul C.; Acton, Ronald T.; Killeen, Anthony A.; McLaren, Gordon D.

In: PLoS One, Vol. 6, No. 3, e17390, 2011.

Research output: Contribution to journalArticle

McLaren, CE, Garner, CP, Constantine, CC, McLachlan, S, Vulpe, CD, Snively, BM, Gordeuk, VR, Nickerson, DA, Cook, JD, Leiendecker-Foster, C, Beckman, KB, Eckfeldt, JH, Barcellos, LF, Murray, JA, Adams, PC, Acton, RT, Killeen, AA & McLaren, GD 2011, 'Genome-wide association study identifies genetic loci associated with iron deficiency', PLoS One, vol. 6, no. 3, e17390. https://doi.org/10.1371/journal.pone.0017390
McLaren CE, Garner CP, Constantine CC, McLachlan S, Vulpe CD, Snively BM et al. Genome-wide association study identifies genetic loci associated with iron deficiency. PLoS One. 2011;6(3). e17390. https://doi.org/10.1371/journal.pone.0017390
McLaren, Christine E. ; Garner, Chad P. ; Constantine, Clare C. ; McLachlan, Stela ; Vulpe, Chris D. ; Snively, Beverly M. ; Gordeuk, Victor R. ; Nickerson, Debbie A. ; Cook, James D. ; Leiendecker-Foster, Catherine ; Beckman, Kenneth B. ; Eckfeldt, John H. ; Barcellos, Lisa F. ; Murray, Joseph A ; Adams, Paul C. ; Acton, Ronald T. ; Killeen, Anthony A. ; McLaren, Gordon D. / Genome-wide association study identifies genetic loci associated with iron deficiency. In: PLoS One. 2011 ; Vol. 6, No. 3.
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