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Genome screens for asthma
Researchers consider multiple susceptibility factors simultaneously
Edward R. Winstead

Researchers seeking susceptibility genes for asthma have identified regions of interest on three human chromosomes based on genome screens involving 266 families from three ethnic groups. Analyses of data on each ethnic group individually yielded different regions. Further, asthma-susceptibility genes on different chromosomes may interact to increase the risk for developing the disease and related conditions, according to a study in The American Journal of Human Genetics.

Nancy J. Cox, of The University of Chicago, and other researchers conducted the genome screens as part of the Collaborative Study on the Genetics of Asthma (CSGA). The 266 families in the study included pairs of siblings that were recruited through one of the study's centers. African Americans, European Americans, and Hispanics participated in the study.

Asthma-susceptibility genes are most likely to reside on regions of chromosomes 5, 12, and 14, according to analyses of data on all families. Ethnic-specific analyses revealed additional hotspots: Regions were implicated on chromosome 11 for the 107 African American families, on chromosome 6 for the 129 European American families, and on chromosome 1 for the 30 Hispanic families. Several of these regions had been linked to asthma in earlier studies.

In addition to the genome-wide screen, the researchers conducted 'conditional analyses' to identify regions that reached levels of statistic significance in the presence of another susceptibility locus. This so-called interactive two-locus analysis revealed potential regions of interest not apparent in the original genome-wide analysis. The relevance, or linkage, of the second locus was conditional on the first locus.

"For example," the researchers write, "conditional analyses based on evidence of linkage at either 11q21 or 14q32 resulted in significantly increased evidence of linkage at 12q22."

Although complex disorders are generally agreed to involve the actions and interactions of many genetic and non-genetic factors, Cox and colleagues write, "primary analyses generally do not consider the effects from multiple susceptibility factors simultaneously." They note, however, that there are "clear examples, in animal studies, of loci showing little or no major effects in a primary analysis but, nevertheless, contributing substantially to the genetics of the trait, when analyzed for gene-gene and/or gene-environment interactions"

The Collaborative Study on the Genetics of Asthma is a multicenter collaborative study supported by the US National Heart, Lung and Blood Institute of the National Institutes of Health.

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Xu, J. et al. Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: Collaborative Study on the Genetics of Asthma. Am J Hum Genet 68, 1437-1446 (June 2001).

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