Genome-wide association study identifies genetic loci associated with iron deficiency.
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 w...
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017390&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Christine E McLaren |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b65e48c2eebe475e8db2cd147aec2f3d |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b65e48c2eebe475e8db2cd147aec2f3d2025-08-20T03:10:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1739010.1371/journal.pone.0017390Genome-wide association study identifies genetic loci associated with iron deficiency.Christine E McLarenChad P GarnerClare C ConstantineStela McLachlanChris D VulpeBeverly M SnivelyVictor R GordeukDebbie A NickersonJames D CookCatherine Leiendecker-FosterKenneth B BeckmanJohn H EckfeldtLisa F BarcellosJoseph A MurrayPaul C AdamsRonald T ActonAnthony A KilleenGordon D McLarenThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017390&type=printable |
| spellingShingle | 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 Genome-wide association study identifies genetic loci associated with iron deficiency. PLoS ONE |
| title | Genome-wide association study identifies genetic loci associated with iron deficiency. |
| title_full | Genome-wide association study identifies genetic loci associated with iron deficiency. |
| title_fullStr | Genome-wide association study identifies genetic loci associated with iron deficiency. |
| title_full_unstemmed | Genome-wide association study identifies genetic loci associated with iron deficiency. |
| title_short | Genome-wide association study identifies genetic loci associated with iron deficiency. |
| title_sort | genome wide association study identifies genetic loci associated with iron deficiency |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017390&type=printable |
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