A genome-wide search for quantitative trait loci contributing to variation in seasonal pollen reactivity.
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).


CONCLUSIONS
These results suggest both substantial genetic overlap and extensive heterogeneity in the genetic basis for the allergic response to seasonal allergens.
Blumenthal
Malcolm N
MN
Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Langefeld
Carl D
CD
Barnes
Kathleen C
KC
Ober
Carole
C
Meyers
Deborah A
DA
King
Richard A
RA
Beaty
Terri H
TH
Beck
Stephanie R
SR
Bleecker
Eugene R
ER
Rich
Stephen S
SS
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D008040:Genetic Linkage; D016678:Genome; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008126:Lod Score; D008285:Major Histocompatibility Complex; D011058:Pollen / Q000276:immunology*; D040641:Quantitative Trait Loci; D012621:Seasons