Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: collaborative study on the genetics of asthma.

Xu J, Meyers DA, Ober C, Blumenthal MN, Mellen B, Barnes KC, King RA, Lester LA, Howard TD, Solway J, Langefeld CD, Beaty TH, Rich SS, Bleecker ER, Cox NJ, Collaborative Study on the Genetics of Asthma
Am J Hum Genet. 2001 68 (6): 1437-46

PMID: 11349227 · PMCID: PMC1226130 · DOI:10.1086/320589

The genomewide screen to search for asthma-susceptibility loci, in the Collaborative Study on the Genetics of Asthma (CSGA), has been conducted in two stages and includes 266 families (199 nuclear and 67 extended pedigrees) from three U.S. populations: African American, European American, and Hispanic. Evidence for linkage with the asthma phenotype was observed for multiple chromosomal regions, through use of several analytical approaches that facilitated the identification of multiple disease loci. Ethnicity-specific analyses, which allowed for different frequencies of asthma-susceptibility genes in each ethnic population, provided the strongest evidence for linkage at 6p21 in the European American population, at 11q21 in the African American population, and at 1p32 in the Hispanic population. Both the conditional analysis and the affected-sib-pair two-locus analysis provided further evidence for linkage, at 5q31, 8p23, 12q22, and 15q13. Several of these regions have been observed in other genomewide screens and linkage or association studies, for asthma and related phenotypes. These results were used to develop a conceptual model to delineate asthma-susceptibility loci and their genetic interactions, which provides a promising basis for initiation of fine-mapping studies and, ultimately, for gene identification.

MeSH Terms (25)

Adolescent Adult Africa Asthma Child Chromosome Mapping Chromosomes, Human Continental Population Groups Ethnic Groups Europe Female Genetic Heterogeneity Genetic Linkage Genetic Markers Genetic Predisposition to Disease Genetic Testing Genotype Humans Lod Score Male Matched-Pair Analysis Molecular Sequence Data Nuclear Family Pedigree United States

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