How strongly are IgE levels inherited, and does the inheritance pattern differ between families?

Details

Researchers studied the genetic aspects of IgE levels in three large pedigrees, many of whose members had atopic sensitivities to ragweed. They analyzed data from 184 people (80 male, 104 female) using the methods of Elston and Stewart, after logarithmic transformation and appropriate adjustment for sex and age effects. Several modes of transmission were fitted to the data.

The environmental model, which assumed equal transmission frequency for all genotypes, clearly did not fit the data (chi-square 23.03, df 3). This suggested a strong hereditary contribution to the distribution of IgE levels. In the pooled data, the hypothesis that a dominant allele determines high IgE levels gave the best fit among the hypotheses examined.

Under a pure polygenic model, estimated heritability was 49.5%. A mixed model combining major-gene and polygenic transmission estimated the polygenic contribution at 11%, but did not significantly improve on the major-gene model. This mixed-model analysis was an approximation biased toward inflating the major-gene component.

When the families were analyzed separately, there was evidence of significant heterogeneity among them. The genetic picture was unclear: one family favored recessive inheritance of high IgE levels, one showed no clear mode, and the third leaned slightly toward dominant inheritance.

The researchers suggested that the mechanism was not as simple as previously thought and that either two alleles or one gene might be involved in determining IgE levels. Overall, the findings were consistent with genetic determination of IgE levels, with heritability estimated at about 50%.