Genome‐wide linkage analyses of total serum IgE using variance components analysis in asthmatic families

Abstract

Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA)

“…Since this previous analysis could reflect a generalized reactivity to multiple allergens, further refinement of the atopic phenotype could clarify as to which of these linkage signals, if any, reflect reactivity to specific mite allergens. 6 In our study, mite sensitivity for the CSGA families gave the strongest support for linkage on chromosomes 19 and 20. In the genome scan for specific atopy, evidence supporting linkage (lod B1.0) occurred on chromosome 19p at D19S591 in Caucasians, which is the same location where we observed evidence of linkage for the mite reactivity phenotype.…”

“…2 Investigation of the general phenotype of skin sensitivity to one or more common aeroallergens has been reported previously for this CSGA data. 6 A complex pattern of the evidence for linkage to several different regions on chromosomes 11q and 20p was observed in this analysis. Multilocus modeling suggested that, in addition to these two chromosomal locations, two other regions (on 10p and 17q) accounted for the majority of evidence for linkage to atopic responses in these CSGA families.…”

“…Genome-wide linkage analyses to identify genes influencing the risk to asthma, 5 total IgE levels 6 and generalized atopy (defined as the presence of at least one positive skin test to a set of common allergens) 7 have been reported previously. Here, we present the analysis of the genome-wide scan using positive skin test response for two asthma-associated perennial allergens, Der pteronyssinus (Der p) and Der farinae (Der f), as the phenotype in a genome-wide scan for susceptibility genes.…”

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

“…Indeed, the 1p31 region has been already reported for linkage to asthma in the Caucasian population of the CSGA study, 22 to atopy 23 and IgE 24 in the Hispanic group of the same study and to IgE in a Dutch population. 25 The 2q32 region was previously detected for IgE in the two German 26 and Dutch 25 genome scans.…”

Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations

“…Higher total IgE levels have also been observed in individuals of African descent compared with individuals of European descent (3,4). Although it is unknown to what extent genetic susceptibility contributes to disparities in risk for atopic asthma, both linkage and association studies have shown evidence of genetic differences among ethnic and racial groups (4)(5)(6)(7).…”