Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

Genes & Immunity volume 6, pages 95–102 (2005)Cite this article

Abstract

In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24–p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22–q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24–p14, 9p22 and 9q22–q34 are more likely to harbor genetic factors specific to AR.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Bousquet J, Van Cauwenberge P, Khaltaev N . Rhinitis and its impact on asthma. J Allergy Clin Immunol 2001; 108 (5 Suppl): S147–S334.

    Article  CAS  PubMed  Google Scholar 

  2. Dold S, Wjst M, von Mutius E, Reitmeir P, Stiepel E . Genetic risk for asthma, rhinitis, and atopic dermatitis. Arch Dis Child 1992; 67: 1018–1022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rasanen M, Laitinen T, Kaprio J, Koskenvuo M, Laitinen LA . Hay fever—a Finnish nationwide study of adolescent twins and their parents. Allergy 1998; 53: 885–890.

    Article  CAS  PubMed  Google Scholar 

  4. Annesi-Maesano I, Cotichini R, Stazi MA . Early gene–environment interaction into asthma and rhinitis comorbidity. Chest 2001; 120: 1755.

    Article  CAS  PubMed  Google Scholar 

  5. Hopper JL, Hannah MC, Macaskill GT, Mathews JD . Twin concordance for a binary trait: III. A bivariate analysis of hay fever and asthma. Genet Epidemiol 1990; 7: 277–289.

    Article  CAS  PubMed  Google Scholar 

  6. Duffy DL, Martin NG, Battistutta D, Hopper JL, Mathews JD . Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis 1990; 142 (Part 1): 1351–1358.

    Article  CAS  PubMed  Google Scholar 

  7. Wills-Karp M, Ewart SL . Time to draw breath: asthma-suceptibility genes are identified. Nat Genet 2004; 5: 376–387.

    Article  CAS  Google Scholar 

  8. Van Eerdewegh P, Little RD, Dupuis J et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002; 418: 426–430.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang Y, Leaves NI, Anderson GG et al. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet 2003; 34: 181–186.

    Article  CAS  PubMed  Google Scholar 

  10. Allen M, Heinzmann A, Noguchi E et al. Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nat Genet 2003; 35: 258–263.

    Article  CAS  PubMed  Google Scholar 

  11. Laitinen T, Polvi A, Rydman P et al. Characterization of a common susceptibility locus for asthma-related traits. Science 2004; 304: 300–304.

    Article  CAS  PubMed  Google Scholar 

  12. Haagerup A, Bjerke T, Schoitz PO, Binderup HG, Dahl R, Kruse TA . Rhinitis—a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24–q27. Eur J Hum Genet 2001; 9: 945–952.

    Article  CAS  PubMed  Google Scholar 

  13. Yokouchi Y, Scibasaki M, Noguchi E et al. A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal rhinitis in Japanese families. Genes Immun 2002; 3: 9–13.

    Article  CAS  PubMed  Google Scholar 

  14. Ober C, Tsalenko A, Parry R, Cox NJ . A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 2000; 67: 1154–1162.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Dizier MH, Besse-Schmittler C, Guilloud-Bataille M et al. Genome screen for asthma and related phenotypes in the French EGEA study. Am J Respir Crit Care Med 2000; 162: 1812–1818.

    Article  CAS  PubMed  Google Scholar 

  16. Bouzigon E, Dizier MH, Krähenbühl C et al. Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families. Hum Mol Genet 2004; 13: 3103–3113.

    Article  CAS  PubMed  Google Scholar 

  17. Annesi-Maesano I, Didier A, Klossek M, Chanal I, Moreau D, Bousquet J . The score for rhinitis (SFAR): a simple and valid assessment method in population studies. Allergy 2002; 57: 107–114.

    Article  CAS  PubMed  Google Scholar 

  18. Abel L, Alcais A, Mallet A . Comparison of four sib-pair linkage methods for analyzing sibships with more than two affecteds: interest of the binomial maximum likelihood approach. Genet Epidemiol 1998; 15: 371–390.

    Article  CAS  PubMed  Google Scholar 

  19. Annesi-Maesano I . Rhinitis and asthma: epidemiological evidence. Allergy Clin Immunol Intern 2001; 13: 1–7.

    Article  Google Scholar 

  20. Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.

    Article  CAS  PubMed  Google Scholar 

  21. Sawcer S, Jones HB, Judge D et al. Empirical genomewide significance levels established by whole genome simulations. Genet Epidemiol 1997; 14: 223–229.

    Article  CAS  PubMed  Google Scholar 

  22. The Collaborative Study on the Genetics of Asthma (CSGA). A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nat Genet 1997; 15: 389–392.

  23. Hizawa N, Freidhoff LR, Chiu YF et al. Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: a genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs. J Allergy Clin Immunol 1998; 102: 436–442.

    Article  CAS  PubMed  Google Scholar 

  24. Mathias RA, Freidhoff LR, Blumenthal MN et al. Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families. Genet Epidemiol 2001; 20: 340–355.

    Article  CAS  PubMed  Google Scholar 

  25. Koppelman GH, Stine OC, Xu J et al. Genome-wide search for atopy susceptibility genes in Dutch families with asthma. J Allergy Clin Immunol 2002; 109: 498–506.

    Article  CAS  PubMed  Google Scholar 

  26. Wjst M, Fischer G, Immervoll T et al. A genome-wide search for linkage to asthma. German Asthma Genetics Group. Genomics 1999; 58: 1–8.

    Article  CAS  PubMed  Google Scholar 

  27. Howard TD, Postma DS, Hawkins GA et al. Fine mapping of an IgE-controlling gene on chromosome 2q: analysis of CTLA4 and CD28. J Allergy Clin Immunol 2002; 110: 743–751.

    Article  CAS  PubMed  Google Scholar 

  28. Hizawa N, Yamaguchi E, Jinushi E et al. Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B. J Allergy Clin Immunol 2001; 108: 74–79.

    Article  CAS  PubMed  Google Scholar 

  29. Bradley M, Söderhäll C, Luthman H et al. Susceptibility loci for atopic dermatitis on chromosomes 3, 13, 15, 17 and 18 in a Swedish population. Hum Mol Genet 2002; 11: 1539–1548.

    Article  CAS  PubMed  Google Scholar 

  30. Ober C, Cox NJ, Abney M et al. Genome-wide search for asthma susceptibility loci in a founder population. Hum Mol Genet 1998; 7: 1393–1398.

    Article  CAS  PubMed  Google Scholar 

  31. Blumenthal MN, Ober C, Beaty TH et al. Genome scan for loci linked to mite sensitivity: the Collaborative study on the genetics of asthma (CSGA). Genes Immun 2004; 5: 226–231.

    Article  CAS  PubMed  Google Scholar 

  32. Ober C, Tsalenko A, Willadsen S et al. Genome-wide screen for atopy susceptibility alleles in the Hutterites. Clin Exp Allergy 1999; 29: S11–S15.

    Google Scholar 

  33. Leynaert B, Neukirch C, Kony S et al. Association between asthma and rhinitis according to atopic sensitization in a population-based study. J Allergy Clin Immunol 2004; 113: 86–93.

    Article  PubMed  Google Scholar 

  34. Kauffmann F, Dizier MH, Annesi-Maesano I et al. EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy)—descriptive characteristics. Clin Exp Allergy 1999; 29 (Suppl 4): 17–21.

    PubMed  Google Scholar 

  35. Kauffmann F, Annesi-Maesano I, Liard R et al. Construction et validation d'un questionnaire en épidémiologie respiratoire. L'exemple du questionnaire de l'étude épidémiologique des facteurs génétiques et environnementaux de l'asthme, l'hyperréactivité bronchique et de l'atopie (EGEA). Rev Mal Resp 2002; 19: 323–333.

    CAS  Google Scholar 

  36. O'Connell J, Weeks E . PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Satsangi J, Parkes M, Louis E et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 1996; 14: 199–202.

    Article  CAS  PubMed  Google Scholar 

  38. Majumder PP, Pal N . Nonrandom segregation: uniformly most powerful test and related considerations. Genet Epidemiol 1987; 4: 277–287.

    Article  CAS  PubMed  Google Scholar 

  39. Alcais A, Philippi A, Abel L . Genetic model-free linkage analysis using the maximum-likelihood-binomial method for categorical traits. Genet Epidemiol 1999; 17 (Suppl 1): S467–S472.

    Article  PubMed  Google Scholar 

  40. Abel L, Muller-Myhsok B . Robustness and power of the maximum-likelihood-binomial and maximum-likelihood-score methods, in multipoint linkage analysis of affected-sibship data. Am J Hum Genet 1998; 63: 638–647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES . Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 1996; 58: 1347–1363.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U535, Hôpital Paul Brousse, Bâtiment Leriche, Villejuif Cedex, France

    M -H Dizier & M Guilloud-Bataille

  2. INSERM EMI 00-06, Evry, France

    E Bouzigon & F Demenais

  3. Centre National de Génotypage, Evry, France

    C Bétard, A Lemainque & M Lathrop

  4. Clinique des maladies respiratoires, INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France

    J Bousquet

  5. Service de pneumologie-allergologie, Hôpital Nord, Marseille, France

    D Charpin

  6. Service de Pneumologie, centre hospitalier Lyon-Sud, Pierre Benite

    F Gormand

  7. INSERM U436, Paris, France

    J Hochez

  8. Centre de diagnostic et traitement de l'asthme, Hôpital Trousseau, Paris, France

    J Just

  9. INSERM U472, Villejuif, France

    N Le Moual, M -P Oryszczyn, F Kauffmann & I Annesi-Maesano

  10. Laboratoire d'exploration fonctionnelle, Hôpital Calmette, Lille, France

    R Matran

  11. INSERM U408, Paris, France

    F Neukirch

  12. Service de pneumologie infantile, Hôpital Necker, Paris, France

    E Paty

  13. Département de Médecine Aigüe Spécialisée, CHU Michallon, Grenoble, France

    I Pin

  14. Service de pneumo-allergologie, Hôpital Ste Marguerite, UPRES EA 3287, Marseille, France

    D Vervloet

Authors
  1. M -H Dizier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Bouzigon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Guilloud-Bataille
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Bétard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Bousquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D Charpin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Gormand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Hochez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Just
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Lemainque
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N Le Moual
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. R Matran
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F Neukirch
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. M -P Oryszczyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. E Paty
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. I Pin
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. D Vervloet
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. F Kauffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. M Lathrop
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. F Demenais
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. I Annesi-Maesano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M -H Dizier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dizier, MH., Bouzigon, E., Guilloud-Bataille, M. et al. Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma. Genes Immun 6, 95–102 (2005). https://doi.org/10.1038/sj.gene.6364163

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364163

Keywords

This article is cited by

Search

Advanced search

Quick links