BACKGROUND: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error. OBJECTIVE: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis. METHODS: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items. RESULTS: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less. CONCLUSION: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.
BACKGROUND: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error. OBJECTIVE: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis. METHODS: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items. RESULTS: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less. CONCLUSION: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.
Authors: Manuel A R Ferreira; Louise O'Gorman; Peter Le Souëf; Paul R Burton; Brett G Toelle; Colin F Robertson; Peter M Visscher; Nicholas G Martin; David L Duffy Journal: Am J Hum Genet Date: 2005-10-14 Impact factor: 11.025