Background: Asthma and atopy represent complex traits for which genetic predisposition has been demonstrated. Pollen sensitivity, whether seasonal or chronic, appears to be a major contributor to the asthmatic phenotype. Objective: Regions of the genome contributing to skin test reactivity to 5 seasonal allergens are to be identified in a genome-wide scan. These regions may be distinct from those contributing to risk for asthma and/or atopy. Methods: In the Collaborative Study on the Genetics of Asthma, 4 sites collected 287 families with 2 or more members with asthma. Reactivity to individual pollens were determined on all family members. A genome scan was performed at 9-centiMorgan intervals, and skin test reactivity to 5 seasonal allergens was the focus of nonparametric genetic linkage analysis. Results: Chromosomal regions that exhibited suggestive linkage (logarithm of the odds >1.18; P < .01) to seasonal pollen reactivity were identified on chromosomes 13q34, 20p12, and 21q21. Evidence of ethnic differences in linkage to seasonal allergens was demonstrated, with support for linkage in African American subjects on chromosomes 8, 10, and 12, in European American subjects on chromosomes 14, 19, 20, and 22, and in Hispanics on chromosome 21. In all families, evidence for linkage of skin test reactivity for Betula, Lolium, and Artemisia was strongest in a region on chromosome 21 that contained the candidate gene, A Disintegrin And Metalloprotease domain 33 (ADAM33). Conclusion: These results suggest both substantial genetic overlap and extensive heterogeneity in the genetic basis for the allergic response to seasonal allergens.
Bibliographical noteFunding Information:
Supported by the following National Institutes of Health grants: U01 HL49612 (JHU), U01 HL49596 and M01 RR00055 (UC), U01 HL59609 and M01 RR00400 (UMN), U01 HL58977, U01 HL49602, U01 HL49609 and M01 RR00600 (University of Maryland and Wake Forest University), HV-48141 (Mammalian Genotyping Service), and HRRC 93-196 (University of New Mexico).
- Genome scan
- Seasonal pollen sensitivity