Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families

R. A. Mathias, L. R. Freidhoff, M. N. Blumenthal, D. A. Meyers, L. Lester, R. King, J. F. Xu, J. Solway, K. C. Barnes, J. Pierce, O. C. Stine, A. Togias, W. Oetting, P. L. Marshik, J. B. Hetmanski, S. K. Huang, E. Ehrlich, G. M. Dunston, F. Malveaux, S. Banks-Schlegel & 5 others N. J. Cox, E. Bleecker, C. Ober, T. H. Beaty, S. S. Rich

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Abstract

Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.

Original languageEnglish
Pages (from-to)340-355
Number of pages16
JournalGenetic Epidemiology
Volume20
Issue number3
DOIs
Publication statusPublished - Apr 10 2001
Externally publishedYes

Fingerprint

Immunoglobulin E
Analysis of Variance
Genome
Chromosomes, Human, Pair 4
Serum
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 2
Asthma
Chromosomes, Human, Pair 20
Quantitative Trait Loci
Skin Tests
African Americans
Hypersensitivity
Genes

Keywords

  • Allergy Index
  • Asthma
  • Linkage
  • Total IgE levels
  • Variance components

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Cite this

Mathias, R. A., Freidhoff, L. R., Blumenthal, M. N., Meyers, D. A., Lester, L., King, R., ... Rich, S. S. (2001). Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families. Genetic Epidemiology, 20(3), 340-355. https://doi.org/10.1002/gepi.5

Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families. / Mathias, R. A.; Freidhoff, L. R.; Blumenthal, M. N.; Meyers, D. A.; Lester, L.; King, R.; Xu, J. F.; Solway, J.; Barnes, K. C.; Pierce, J.; Stine, O. C.; Togias, A.; Oetting, W.; Marshik, P. L.; Hetmanski, J. B.; Huang, S. K.; Ehrlich, E.; Dunston, G. M.; Malveaux, F.; Banks-Schlegel, S.; Cox, N. J.; Bleecker, E.; Ober, C.; Beaty, T. H.; Rich, S. S.

In: Genetic Epidemiology, Vol. 20, No. 3, 10.04.2001, p. 340-355.

Research output: Contribution to journalArticle

Mathias, RA, Freidhoff, LR, Blumenthal, MN, Meyers, DA, Lester, L, King, R, Xu, JF, Solway, J, Barnes, KC, Pierce, J, Stine, OC, Togias, A, Oetting, W, Marshik, PL, Hetmanski, JB, Huang, SK, Ehrlich, E, Dunston, GM, Malveaux, F, Banks-Schlegel, S, Cox, NJ, Bleecker, E, Ober, C, Beaty, TH & Rich, SS 2001, 'Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families', Genetic Epidemiology, vol. 20, no. 3, pp. 340-355. https://doi.org/10.1002/gepi.5
Mathias RA, Freidhoff LR, Blumenthal MN, Meyers DA, Lester L, King R et al. Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families. Genetic Epidemiology. 2001 Apr 10;20(3):340-355. https://doi.org/10.1002/gepi.5
Mathias, R. A. ; Freidhoff, L. R. ; Blumenthal, M. N. ; Meyers, D. A. ; Lester, L. ; King, R. ; Xu, J. F. ; Solway, J. ; Barnes, K. C. ; Pierce, J. ; Stine, O. C. ; Togias, A. ; Oetting, W. ; Marshik, P. L. ; Hetmanski, J. B. ; Huang, S. K. ; Ehrlich, E. ; Dunston, G. M. ; Malveaux, F. ; Banks-Schlegel, S. ; Cox, N. J. ; Bleecker, E. ; Ober, C. ; Beaty, T. H. ; Rich, S. S. / Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families. In: Genetic Epidemiology. 2001 ; Vol. 20, No. 3. pp. 340-355.
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