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Clinical & Experimental Allergy

Familial aggregation of food allergy and sensitization to food allergens: a family-based study

Authors

  • H.-J. Tsai,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
    2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • R. Kumar,

    1. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
    2. Division of Allergy and Immunology, Children's Memorial Hospital and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • J. Pongracic,

    1. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
    2. Division of Allergy and Immunology, Children's Memorial Hospital and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • X. Liu,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
    2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • R. Story,

    1. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
    2. Division of Allergy and Immunology, Children's Memorial Hospital and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • Y. Yu,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
    2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • D. Caruso,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
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  • J. Costello,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
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  • A. Schroeder,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
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  • Y. Fang,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
    2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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  • H. Demirtas,

    1. Division of Epidemiology and Biostatistics, University of Illinois at Chicago, School of Public Health, Chicago, IL, USA,
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  • K. E. Meyer,

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
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  • M. R. G. O'Gorman,

    1. The Diagnostic Immunology and Flow Cytometry Laboratory, Children's Memorial Hospital and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    2. Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • X. Wang

    1. Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA,
    2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA,
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Correspondence:
Hui-Ju Tsai, Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. E-mail: htsai@childrensmemorial.org, h-tsai@northwestern.edu

Summary

Background The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown.

Objective This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens.

Methods This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut-offs for geqslant R: gt-or-equal, slanted95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements.

Results FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2–5.6, P=0.01). There were significant and positive associations among family members (father–offspring, mother–offspring, index–other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens.

Conclusion This family-based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE-mediated FA.

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