Segregation analysis of IgE levels in 335 French families (EGEA) using different strategies to correct for the ascertainment through a correlated trait (asthma)

Francesca Sampogna, Florence Demenais, Joelle Hochez, Marie Pierre Oryszczyn, Jean Maccario, Francine Kauffmann, Josué Feingold, Marie Hélène Dizier

Research output: Contribution to journalArticlepeer-review

Abstract

The main objective of this study was to search for a major gene controlling total serum immunoglobulin E (IgE) levels, an intermediate phenotype for asthma and allergy. We studied 335 French nuclear families of the EGEA study (Epidemiological study of the Genetics and Environment of Asthma), ascertained through asthmatic probands (123 are parents in the family, 212 children). Segregation analyses were performed by regressive models, which can take into account a major gene effect, various sources of familial covariation (genetic and/or environmental) as well as measured risk factors (i.e., age, sex, smoking habits). Different strategies were considered to account for the mode of ascertainment of the families through a correlated trait (asthma): the ascertainment mode was either ignored (strategy A) or taken into account by adjusting IgE levels for the position in the family, i.e., probands, blood relatives, spouses (strategy B) or excluding the asthmatic children-probands and computing the likelihood of each family conditionally on parents' IgE levels (strategy C). Whereas a major gene effect could not be detected with strategy A, strategies B and C showed evidence for the transmission of a dominant major gene for high IgE levels, which was more significant with strategy B. This gene does not interact with any of the covariates and is responsible for ~15% of IgE variation (the allele frequency is 0.65). (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)128-142
Number of pages15
JournalGenetic Epidemiology
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2000

Keywords

  • Correction for ascertainment mode
  • Immunoglobulin E
  • Regressive model
  • Segregation analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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