Skip to main content
Log in

Sex differences in heritability of sensitization to Blomia tropicalis in asthma using regression of offspring on midparent (ROMP) methods

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

A genetic basis for asthma- and atopy-related quantitative traits, such as allergen-specific immunoglobulin E (IgE) levels, has been suggested by the observed familial aggregation of these traits in temperate climates. Less information is available for tropical climates, where different allergens may predominate. Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but heritability of B. tropicalis sensitivity and the impact of age, sex, and other environmental covariates on heritability have not been widely explored. Total and specific IgE levels were measured by immunochemiluminescent assay in 481 members of 29 Barbadian families (comprised of 340 parent-offspring trios or pairs) ascertained through two asthmatic siblings. Trait heritability was estimated using regression of offspring on mid-parent (ROMP) and pairwise correlation analysis of unadjusted IgE levels and on residual values after adjustment for covariates. Heritability of IgE levels to the major antigen of B. tropicalis (Blo t M) estimated by ROMP in 180 complete parent-offspring trios was 0.56. Heritability was consistently greater for male offspring than for female offspring. Similar sex-specific patterns were observed for specific IgE to Dermatophagoides pteronyssinus and total IgE levels and were relatively unaffected by adjustment for covariates. Pairwise correlational analyses of specific and total IgE levels showed similar results. Moderate heritability of Blo t M IgE levels was detected in these Barbadian families and was greater for sons than daughters. Adjustment for covariates had minimal impact. This suggests that future investigations of genetic determinants of IgE levels should include approaches that allow for potential sex differences in their expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

References

  • Abney M, McPeek MS, Ober C (2001) Broad and narrow heritabilities of quantitative traits in a founder population. Am J Hum Genet 68:1302–1307

    Article  CAS  PubMed  Google Scholar 

  • Annesi I, Oryszczyn MP, Frette C, Neukirch F, Orvoen-Frija E, Kauffmann F (1992) Total circulating IgE and FEV1 in adult men. An epidemiologic longitudinal study. Chest 101:642–648

    CAS  PubMed  Google Scholar 

  • Barbee RA, Halonen M, Lebowitz M, Burrows B (1981) Distribution of IgE in a community population sample: correlations with age, sex, and allergen skin test reactivity. J Allergy Clin Immunol 68:106–111

    CAS  PubMed  Google Scholar 

  • Barnes KC, Neely JD, Duffy DL, Freidhoff LR, Breazeale DR, Schou C, Naidu RP, Levett PN, Renault B, Kucherlapati R, Iozzino S, Ehrlich E, Beaty TH, Marsh DG (1996) Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics 37:41–50

    Article  CAS  PubMed  Google Scholar 

  • Barnes KC, Freidhoff LR, Horowitz EM, Mathias RA, Mulkern DM, Bonacum JT, Goldman MH, Polito AJ, Saini SS, Marsh DG, Beaty TH, Togias A (1999) Physician-derived asthma diagnoses made on the basis of questionnaire data are in good agreement with interview-based diagnoses and are not affected by objective tests. J Allergy Clin Immunol 104:791–796

    CAS  PubMed  Google Scholar 

  • Blumenthal MN (2000) Genetics of asthma and allergy. Allergy Asthma Proc 21:55–59

    CAS  PubMed  Google Scholar 

  • Blumenthal MN, Banks-Schlegel S, Bleecker ER, Marsh DG, Ober C (1995) Collaborative studies on the genetics of asthma — National Heart, Lung and Blood Institute. Clin Exp Allergy 25 (Suppl 2):29–32

    Google Scholar 

  • Boomsma DI, Snieder H, de Geus EJ, van Doornen LJ (1998) Heritability of blood pressure increases during mental stress. Twin Res 1:15–24

    CAS  PubMed  Google Scholar 

  • Burrows B, Halonen M, Barbee RA, Lebowitz MD (1981) The relationship of serum immunoglobulin E to cigarette smoking. Am Rev Respir Dis 124:523–525

    CAS  PubMed  Google Scholar 

  • Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG (1989) Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 320:271–277

    CAS  PubMed  Google Scholar 

  • Burrows B, Martinez FD, Cline MG, Lebowitz MD (1995) The relationship between parental and children's serum IgE and asthma. Am J Respir Crit Care Med 152:1497–1500

    CAS  PubMed  Google Scholar 

  • Chew FT, Yi FC, Chua KY, Fernandez-Caldas E, Arruda LK, Chapman MD, Lee BW (1999) Allergenic differences between the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus. Clin Exp Allergy 29:982–988

    Article  CAS  PubMed  Google Scholar 

  • Ciba-Corning (1990) Specific IgE: Magic Lite SQ. Ciba-Corning Diagnostics, Medfield, Massachusetts

    Google Scholar 

  • Clarke P, Jardine R, Martin NG, Stark AE, Walsh RJ (1980) Sex differences in the inheritance of some anthropometric characters in twins. Acta Genet Med Gemellol (Roma) 29:171–192

    Google Scholar 

  • Cookson WO, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA, Faux JA, Julier C, Nakumura Y, Nakumura Y (1992) Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 340:381–384

    CAS  PubMed  Google Scholar 

  • Cooper DN, Nussbaum RL, Michael Krawczak M (2002) Proposed guidelines for papers describing DNA polymorphism-disease associations. Hum Genet 110:207–208

    Google Scholar 

  • Deichmann KA, Starke B, Schlenther S, Heinzmann A, Sparholt SH, Forster J, Kuehr J (1999) Linkage and association studies of atopy and the chromosome 11q13 region. J Med Genet 36:379–382

    CAS  PubMed  Google Scholar 

  • den Dunnen JT, Antonarakis SE (2001) Nomenclature for the description of human sequence variations. Hum Genet 109:121–124

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Doull IJ (1996) Maternal inheritance of atopy? Clin Exp Allergy 26:613–615

    CAS  PubMed  Google Scholar 

  • Duffy DL (1997) Genetic epidemiology of asthma. Epidemiol Rev 19:129–143

    CAS  PubMed  Google Scholar 

  • Fisher RA (1918) The correlation between relatives on the supposition of Mendelian inheritance. Trans Roy Soc Edinburgh 52:399–433

    Google Scholar 

  • Freidhoff LR, Meyers DA, Marsh DG (1984) A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population. II. The associations among skin sensitivity, total serum IgE, age, sex, and the reporting of allergies in a stratified random sample. J Allergy Clin Immunol 73:490–499

    CAS  PubMed  Google Scholar 

  • Grundbacher FJ, Massie FS (1985) Levels of immunoglobulin G, M, A, and E at various ages in allergic and nonallergic black and white individuals. J Allergy Clin Immunol 75:651–658

    CAS  PubMed  Google Scholar 

  • Hasstedt SJ, Meyers DA, Marsh DG (1983) Inheritance of immunoglobulin E: genetic model fitting. Am J Med Genet 14:61–66

    CAS  PubMed  Google Scholar 

  • Holloway JW, Beghe B, Holgate ST (1999) The genetic basis of atopic asthma. Clin Exp Allergy 29:1023–1032

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Gagnon J, Rice T, Perusse L, Leon AS, Skinner JS, Wilmore JH, Bouchard C, Rao DC (2001) Familial resemblance for free androgens and androgen glucuronides in sedentary black and white individuals: the HERITAGE Family Study. Health, risk factors, exercise training and genetics. J Endocrinol 170:485–492

    CAS  PubMed  Google Scholar 

  • Jacobsen HP, Herskind AM, Nielsen BW, Husby S (2001) IgE in unselected like-sexed monozygotic and dizygotic twins at birth and at 6 to 9 years of age: high but dissimilar genetic influence on IgE levels. J Allergy Clin Immunol 107:659–663

    Article  PubMed  Google Scholar 

  • Jarvis D, Luczynska C, Chinn S, Burney P (1995) The association of age, gender and smoking with total IgE and specific IgE. Clin Exp Allergy 25:1083–1091

    CAS  PubMed  Google Scholar 

  • Kacprazak-Bergman I (1994) Sexual dimorphism of heritability of immunoglobulin levels. Ann Hum Biol 21:563–569

    CAS  PubMed  Google Scholar 

  • Lynch M, Walsh B (1999) Genetics and analysis of quantitative traits. Sinauer Associates, Sunderland, Massachusetts

  • Manolio TA, Barnes KC, Naidu RP, Levett P, Beaty T, Wilson AF (2003) Correlates of sensitization to B. tropicalis and D. pteronyssinus in asthma in Barbados. Int Arch Allergy Immunol 131:119–126

    Article  CAS  PubMed  Google Scholar 

  • Marsh DG, Neely JD, Breazeale DR, Ghosh B, Friedhoff LR, Schou C, Beaty TH (1995) Total serum IgE levels and chromosome 5q. Clin Exp Allergy 25 (Suppl 2):79–83

    PubMed  Google Scholar 

  • McIlhany ML, Shaffer JW, Hines EA Jr (1975) The heritability of blood pressure: an investigation of 200 pairs of twins using the cold pressor test. Johns Hopkins Med J 136:57–64

    CAS  PubMed  Google Scholar 

  • Meyers DA, Beaty TH, Freidhoff LR, Marsh DG (1987) Inheritance of total serum IgE (basal levels) in man. Am J Hum Genet 41:51–62

    CAS  PubMed  Google Scholar 

  • National Asthma Education Program (1991) National Asthma Education Program Expert Panel Report. National Heart, Lung, and Blood Institute, Bethesda, Md., Publication no. 91-3042A

  • Ober C, Abney M, McPeek MS (2001) The genetic dissection of complex traits in a founder population. Am J Hum Genet 69:1068–1079

    Article  CAS  PubMed  Google Scholar 

  • Omenaas E, Bakke P, Elsayed S, Hanoa R, Gulsvik A (1994) Total and specific serum IgE levels in adults: relationship to sex, age and environmental factors. Clin Exp Allergy 24:530–539

    CAS  PubMed  Google Scholar 

  • Orren A, Dowdle EB (1975) The effects of sex and age on serum IgE concentrations in three ethnic groups. Int Arch Allergy Appl Immunol 48:824–835

    CAS  PubMed  Google Scholar 

  • Orren A, Walls RS, Dowdle EB (1975) Serum immunoglobulin E concentrations of allergic patients and blood donors. Influence of allergy, sex and race on IgE values. S Afr Med J 49:1387–1390

    CAS  PubMed  Google Scholar 

  • Oryszczyn MP, Annesi-Maesano I, Charpin D, Paty E, Maccario J, Kauffmann F (2000) Relationships of active and passive smoking to total IgE in adults of the Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). Am J Respir Crit Care Med 161:1241–1246

    CAS  PubMed  Google Scholar 

  • Palmer LJ, Burton PR, Faux JA, James AL, Musk AW, Cookson WO (2000a) Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness. Am J Respir Crit Care Med 161:1836–1843

    CAS  PubMed  Google Scholar 

  • Palmer LJ, Burton PR, James AL, Musk AW, Cookson WO (2000b) Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families. Eur J Hum Genet 8:853–860

    Article  CAS  PubMed  Google Scholar 

  • Perusse L, Rice T, Despres JP, Bergeron J, Province MA, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C (1997) Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study. Arterioscler Thromb Vasc Biol 17:3263–3269

    PubMed  Google Scholar 

  • Plaschke P, Janson C, Norrman E, Bjornsson E, Lundback B, Lindholm N, Rosenhall L, Jarvholm B, Boman G (1996) Skin prick tests and specific IgE in adults from three different areas of Sweden. Allergy 51:461–472

    CAS  PubMed  Google Scholar 

  • Poulsen P, Vaag A, Kyvik K, Beck-Nielsen H (2001) Genetic versus environmental aetiology of the metabolic syndrome among male and female twins. Diabetologia 44:537–543

    Article  CAS  PubMed  Google Scholar 

  • Povey S, Lovering R, Bruford E, Wright M, Lush M, Wain H (2001) The HUGO Gene Nomenclature Committee (HGNC). Hum Genet 109:678–680

    CAS  PubMed  Google Scholar 

  • Puerta L, Fernandez-Caldas E, Mercado D, Lockey RF, Caraballo LR (1996) Sequential determinations of Blomia tropicalis allergens in mattress and floor dust samples in a tropical city. J Allergy Clin Immunol 97:689–691

    CAS  PubMed  Google Scholar 

  • Pugh E, Papanicolaou GJ, Justice CM, Roy-Gagnon MH, Sorant AJ, Kingman A, Wilson AF (2001) Comparison of variance components, ANOVA and regression of offspring on mid-parent methods for SNP markers. Genet Epidemiol 21 (Suppl 1):S794–S799

    PubMed  Google Scholar 

  • Rice T, Vogler GP, Perusse L, Bouchard C, Rao DC (1989) Cardiovascular risk factors in a French Canadian population: resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates. Genet Epidemiol 6:571–588

    CAS  PubMed  Google Scholar 

  • S.A.G.E. (1997) Statistical Analysis for Genetic Epidemiology, Release 3.1. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland

  • SAS Institute (1990) SAS Procedures Guide, Version 6, Third Edition. SAS Institute, Cary, N.C.

  • Sherrill DL, Halonen M, Burrows B (1994) Relationships between total serum IgE, atopy, and smoking: a twenty-year follow-up analysis. J Allergy Clin Immunol 94:954–962

    CAS  PubMed  Google Scholar 

  • Shirakawa T, Kusaka Y, Morimoto K (1992) Combined effect of smoking habits and occupational exposure to hard metal on total IgE antibodies. Chest 101:1569–1576

    CAS  PubMed  Google Scholar 

  • Shirakawa T, Morimoto K (1993) Effect of lifestyle on levels of specific IgE antibodies. Allergy 48:177–182

    CAS  PubMed  Google Scholar 

  • Shirakawa T, Hashimoto T, Furuyama J, Takeshita T, Morimoto K (1994) Linkage between severe atopy and chromosome 11q13 in Japanese families. Clin Genet 46:228–232

    CAS  PubMed  Google Scholar 

  • Silventoinen K, Kaprio J, Lahelma E, Koskenvuo M (2000) Relative effect of genetic and environmental factors on body height: differences across birth cohorts among Finnish men and women. Am J Public Health 90:627–630

    CAS  PubMed  Google Scholar 

  • Solter D (1988) Differential imprinting and expression of maternal and paternal genomes. Annu Rev Genet 22:127–146

    Article  CAS  PubMed  Google Scholar 

  • Sporik R, Chapman MD, Platts-Mills TA (1992) House dust mite exposure as a cause of asthma. Clin Exp Allergy 22:897–906

    CAS  PubMed  Google Scholar 

  • Strachan DP, Wong HJ, Spector TD (2001) Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins. J Allergy Clin Immunol 108:901–907

    Article  CAS  PubMed  Google Scholar 

  • Tovey ER, Sluyter R, Duffy DL, Britton WJ (1998) Immunoblotting analysis of twin sera provides evidence for limited genetic control of specific IgE to house dust mite allergens. J Allergy Clin Immunol 101:491–497

    CAS  PubMed  Google Scholar 

  • Villar T, Holgates T (1994) IgE, smoking and lung function. Clin Exp Allergy 24:508–510

    CAS  PubMed  Google Scholar 

  • Warren CP, Holford-Strevens V, Wong C, Manfreda J (1982) The relationship between smoking and total immunoglobulin E levels. J Allergy Clin Immunol 69:370–375

    CAS  PubMed  Google Scholar 

  • Young RP, Hart BJ, Merrett TG, Read AF, Hopkin JM (1992) House dust mite sensitivity: interaction of genetics and allergen dosage. Clin Exp Allergy 22:205–211

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank the families in Barbados for their generous participation in this study; the physicians and staff of the Black Rock, Sir Winston Scott, Randal Phillips, Maurice Byer, Six Cross Roads, and St. John polyclinics and the Accident and Emergency Department, Queen Elizabeth Hospital; the staff of the Leptospira Laboratory, Barbados, for their technical support; and the Ministry of Health, Barbados, for permission to conduct this study. We are especially grateful to Maria Stockton for assistance with the fieldwork in Barbados, and for technical support with the Barbados data by Rasika A. Mathias, Daniel R. Breazeale, Xielun Xue, Liu Xin, John Neely, Dana Mulkern and Suzen Moeller. Dr. Barnes received support in this work from NIH Grant 1 R01 AI20059 and the Asthma and Allergy Foundation of America. Some of the results of this paper were obtained using the program package S.A.G.E., which is supported by a US Public Health Service Resource Grant (1 P41 RR03655) from the National Center for Research Resources.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Teri A. Manolio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manolio, T.A., Barnes, K.C., Beaty, T.H. et al. Sex differences in heritability of sensitization to Blomia tropicalis in asthma using regression of offspring on midparent (ROMP) methods. Hum Genet 113, 437–446 (2003). https://doi.org/10.1007/s00439-003-1005-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-003-1005-6

Keywords

Navigation