A genome-wide linkage scan for iron phenotype quantitative trait loci: The HEIRS family study

Ronald T. Acton, B. M. Snively, J. C. Barton, C. E. McLaren, P. C. Adams, S. S. wRich, J. H. Eckfeldt, Richard Press, P. Sholinsky, C. Leiendecker-Foster, G. D. McLaren, M. R. Speechley, E. L. Harris, F. W. Dawkins, V. R. Gordeuk

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) =2.08, p =0.001) and of UIBC (LOD =9.52), TS (LOD =4.78), and SF (LOD =2.75) to the chromosome 6p region containing HFE (each p <0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD =2.63, p =0.0007) and of UIBC to chromosome 5q (LOD =2.12, p =0.002) and to chromosome 17q (LOD =2.19, p =0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.

Original languageEnglish (US)
Pages (from-to)518-529
Number of pages12
JournalClinical Genetics
Volume71
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Quantitative Trait Loci
Iron
Genome
Ferritins
Phenotype
Chromosomes
Hemochromatosis
Transferrin
Serum
Iron Overload
Microsatellite Repeats
Genotype

Keywords

  • Ferritin
  • Hemochromatosis
  • Iron
  • Transferrin saturation
  • Unsaturated iron-binding capacity

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Acton, R. T., Snively, B. M., Barton, J. C., McLaren, C. E., Adams, P. C., wRich, S. S., ... Gordeuk, V. R. (2007). A genome-wide linkage scan for iron phenotype quantitative trait loci: The HEIRS family study. Clinical Genetics, 71(6), 518-529. https://doi.org/10.1111/j.1399-0004.2007.00804.x

A genome-wide linkage scan for iron phenotype quantitative trait loci : The HEIRS family study. / Acton, Ronald T.; Snively, B. M.; Barton, J. C.; McLaren, C. E.; Adams, P. C.; wRich, S. S.; Eckfeldt, J. H.; Press, Richard; Sholinsky, P.; Leiendecker-Foster, C.; McLaren, G. D.; Speechley, M. R.; Harris, E. L.; Dawkins, F. W.; Gordeuk, V. R.

In: Clinical Genetics, Vol. 71, No. 6, 06.2007, p. 518-529.

Research output: Contribution to journalArticle

Acton, RT, Snively, BM, Barton, JC, McLaren, CE, Adams, PC, wRich, SS, Eckfeldt, JH, Press, R, Sholinsky, P, Leiendecker-Foster, C, McLaren, GD, Speechley, MR, Harris, EL, Dawkins, FW & Gordeuk, VR 2007, 'A genome-wide linkage scan for iron phenotype quantitative trait loci: The HEIRS family study', Clinical Genetics, vol. 71, no. 6, pp. 518-529. https://doi.org/10.1111/j.1399-0004.2007.00804.x
Acton, Ronald T. ; Snively, B. M. ; Barton, J. C. ; McLaren, C. E. ; Adams, P. C. ; wRich, S. S. ; Eckfeldt, J. H. ; Press, Richard ; Sholinsky, P. ; Leiendecker-Foster, C. ; McLaren, G. D. ; Speechley, M. R. ; Harris, E. L. ; Dawkins, F. W. ; Gordeuk, V. R. / A genome-wide linkage scan for iron phenotype quantitative trait loci : The HEIRS family study. In: Clinical Genetics. 2007 ; Vol. 71, No. 6. pp. 518-529.
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AU - Adams, P. C.

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AU - Eckfeldt, J. H.

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AU - Sholinsky, P.

AU - Leiendecker-Foster, C.

AU - McLaren, G. D.

AU - Speechley, M. R.

AU - Harris, E. L.

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N2 - Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) =2.08, p =0.001) and of UIBC (LOD =9.52), TS (LOD =4.78), and SF (LOD =2.75) to the chromosome 6p region containing HFE (each p <0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD =2.63, p =0.0007) and of UIBC to chromosome 5q (LOD =2.12, p =0.002) and to chromosome 17q (LOD =2.19, p =0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.

AB - Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) =2.08, p =0.001) and of UIBC (LOD =9.52), TS (LOD =4.78), and SF (LOD =2.75) to the chromosome 6p region containing HFE (each p <0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD =2.63, p =0.0007) and of UIBC to chromosome 5q (LOD =2.12, p =0.002) and to chromosome 17q (LOD =2.19, p =0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.

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