Evidence for major genetic control of wheeze in relation to history of respiratory allergy: Humboldt family study

Abstract

We report the results of segregation analyses for wheeze before and after a history of respiratory allergy was taken into consideration. The analyses were based on data from 309 nuclear families with 1,053 individuals living in the town of Humboldt, Saskatchewan in 1993, and were performed by using the REGD program of the SAGE package. For adults, information on wheeze and history of respiratory allergy was provided by themselves, and for children, by their parents. Segregation analyses were first conducted before adjustment for history of respiratory allergy. Other covariates were adjusted including sex, current smoking, household exposure to tobacco smoke, and type of house. A single locus model with residual familial effects fit the data well, but none of the Mendelian models (recessive, dominant, and codominant) could be distinguished. The no-parent-offspring-transmission hypothesis was rejected. However, when the variable of respiratory allergy was included in the models as a covariate, both Mendelian and environmental hypotheses were rejected. The Mendelian model had a relatively lower value of Akaike's Information Criterion than did the environmental model (1095.56 versus 1111.24). The data suggest that a single locus gene explains a portion of wheeze that is related to respiratory allergy, and that common environmental factors and/or polygenes also account for a certain familial aggregation of wheeze.

Segregation analyses of asthma and respiratory allergy: The Humboldt family study

“…However, the no major gene effect models were not rejected after adjusting for history of respiratory allergy. These results were similar to previous findings of wheeze based on data from the Humboldt Family Study, where the familial effects were related to history of respiratory allergy [Chen et al, 1998]. Although wheeze is an important clinical phenotype of asthma, these two conditions are not equivalent, and only some wheezing children have or develop asthma [Sherman et al, 1990; Martinez et al, 1995].…”

“…We conducted a family study in the town of Humboldt, Saskatchewan, in 1993, and ascertained young families through parents who reported having at least one child between ages 6 and 17 years living in the town [Chen et al, 1998, 1999b]. Canvassers contacted all households within the town and left a questionnaire for all adults aged 18–74 years [Chen et al, 1995].…”

“…In a previous analysis of 309 nuclear families, Chen et al [1998] performed a segregation analysis for wheeze, an important clinical characteristic of asthma. Before a history of respiratory allergy was included as a covariate, the data showed that the transmission parameters for a major type were not significantly different from their Mendelian expectations and the hypothesis of a nontransmitted major factor was rejected, suggesting that a major gene influences the expression of wheeze.…”

Asthma Genetics and Intermediate Phenotypes: A Review From Twin Studies

“…The model which fits the data best is the one which adequately describes the segregation of a trait in the families (Cantor & Rotter, 1992;Khoury et al, 1993). Many segregation analyses on asthma have been carried out mostly by using questionnaires (Chen et al, 1998;European Community Respiratory Health Group, 1997;Holberg et al, 1996;Jenkins et al, 1997;Lawrence et al, 1994) and total immunoglobulin E (Gerrard et al, 1978;Hasstedt et al, 1983;Meyers et al, 1987;Panhuysen & Meyers, 1996) Inflammatory process in asthma: allergen uptake and processing by dendritic cells, presentation of peptides to the T-cell receptor, different molecules provides a signal for the Th-0 cel to differentiate into Th-1 or Th-2 cells. These cells have the ability to produce cytokines which are involved in the pathogenesis of asthma (Th-2).…”

The importance of genetic influences in asthma

“…Common environmental and polygenetic effects also contribute to familial aggregation of wheeze [41]. However, it is debatable as to whether wheeze is equivalent to asthma since only a small proportion of wheezing children may actually develop asthma [25,51].…”