Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations

Christine E. McLaren; Stela McLachlan; Chad P. Garner; Chris D. Vulpe; Victor R. Gordeuk; John H. Eckfeldt; Paul C. Adams; Ronald T. Acton; Joseph A. Murray; Catherine Leiendecker-Foster; Beverly M. Snively; Lisa F. Barcellos; James D. Cook; Gordon D. McLaren

doi:10.1371/journal.pone.0038339

Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations

Christine E. McLaren^*, Stela McLachlan, Chad P. Garner, Chris D. Vulpe, Victor R. Gordeuk, John H. Eckfeldt, Paul C. Adams, Ronald T. Acton, Joseph A. Murray, Catherine Leiendecker-Foster, Beverly M. Snively, Lisa F. Barcellos, James D. Cook, Gordon D. McLaren

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged > 25 y and women >50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) 100 mu g/L in men, SF>50 mu g/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7x10(-6)) and replicated in African Americans (p = 0.0012). Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p <4.4x10(-5)); six SNPs replicated in other ethnicities (p

Original language	English
Article number	38339
Number of pages	11
Journal	PLoS ONE
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0038339
Publication status	Published - 22 Jun 2012

Keywords

OVERLOAD SCREENING HEIRS
GENOME-WIDE ASSOCIATION
HEREDITARY HEMOCHROMATOSIS
TRANSFERRIN RECEPTOR
TMPRSS6 GENE
DEFICIENCY
ANEMIA
HOMEOSTASIS
MUTATIONS
ASSAY

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McLaren, C. E., McLachlan, S., Garner, C. P., Vulpe, C. D., Gordeuk, V. R., Eckfeldt, J. H., Adams, P. C., Acton, R. T., Murray, J. A., Leiendecker-Foster, C., Snively, B. M., Barcellos, L. F., Cook, J. D., & McLaren, G. D. (2012). Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations. PLoS ONE, 7(6), [38339]. https://doi.org/10.1371/journal.pone.0038339

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abstract = "The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged > 25 y and women >50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) 100 mu g/L in men, SF>50 mu g/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7x10(-6)) and replicated in African Americans (p = 0.0012). Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p <4.4x10(-5)); six SNPs replicated in other ethnicities (p",

keywords = "OVERLOAD SCREENING HEIRS, GENOME-WIDE ASSOCIATION, HEREDITARY HEMOCHROMATOSIS, TRANSFERRIN RECEPTOR, TMPRSS6 GENE, DEFICIENCY, ANEMIA, HOMEOSTASIS, MUTATIONS, ASSAY",

author = "McLaren, {Christine E.} and Stela McLachlan and Garner, {Chad P.} and Vulpe, {Chris D.} and Gordeuk, {Victor R.} and Eckfeldt, {John H.} and Adams, {Paul C.} and Acton, {Ronald T.} and Murray, {Joseph A.} and Catherine Leiendecker-Foster and Snively, {Beverly M.} and Barcellos, {Lisa F.} and Cook, {James D.} and McLaren, {Gordon D.}",

year = "2012",

month = jun,

day = "22",

doi = "10.1371/journal.pone.0038339",

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McLaren, CE, McLachlan, S, Garner, CP, Vulpe, CD, Gordeuk, VR, Eckfeldt, JH, Adams, PC, Acton, RT, Murray, JA, Leiendecker-Foster, C, Snively, BM, Barcellos, LF, Cook, JD & McLaren, GD 2012, 'Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations', PLoS ONE, vol. 7, no. 6, 38339. https://doi.org/10.1371/journal.pone.0038339

TY - JOUR

T1 - Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations

AU - McLaren, Christine E.

AU - McLachlan, Stela

AU - Garner, Chad P.

AU - Vulpe, Chris D.

AU - Gordeuk, Victor R.

AU - Eckfeldt, John H.

AU - Adams, Paul C.

AU - Acton, Ronald T.

AU - Murray, Joseph A.

AU - Leiendecker-Foster, Catherine

AU - Snively, Beverly M.

AU - Barcellos, Lisa F.

AU - Cook, James D.

AU - McLaren, Gordon D.

PY - 2012/6/22

Y1 - 2012/6/22

N2 - The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged > 25 y and women >50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) 100 mu g/L in men, SF>50 mu g/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7x10(-6)) and replicated in African Americans (p = 0.0012). Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p <4.4x10(-5)); six SNPs replicated in other ethnicities (p

AB - The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged > 25 y and women >50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) 100 mu g/L in men, SF>50 mu g/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7x10(-6)) and replicated in African Americans (p = 0.0012). Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p <4.4x10(-5)); six SNPs replicated in other ethnicities (p

KW - OVERLOAD SCREENING HEIRS

KW - GENOME-WIDE ASSOCIATION

KW - HEREDITARY HEMOCHROMATOSIS

KW - TRANSFERRIN RECEPTOR

KW - TMPRSS6 GENE

KW - DEFICIENCY

KW - ANEMIA

KW - HOMEOSTASIS

KW - MUTATIONS

KW - ASSAY

U2 - 10.1371/journal.pone.0038339

DO - 10.1371/journal.pone.0038339

M3 - Article

VL - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - 38339

ER -

Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations

Abstract

Keywords

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