TY - JOUR
T1 - Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. Populations
T2 - Collaborative study on the genetics of asthma
AU - Collaborative Study on the Genetics of Asthma
AU - Xu, Jianfeng
AU - Meyers, Deborah A.
AU - Ober, Carole
AU - Blumenthal, Malcolm N.
AU - Mellen, Beverly
AU - Barnes, Kathleen C.
AU - Lester, Lucille A.
AU - Howard, Timothy D.
AU - Solway, Julian
AU - Langefeld, Carl D.
AU - Beaty, Terri H.
AU - Cox, Nancy J.
N1 - Funding Information:
This study was supported by the following NIH grants: HL49612 (to Johns Hopkins University), HL49596 and MR1 RR00055 (to the University of Chicago), HL49602 (to the University of Maryland; now Wake Forest University), HL49609 and MO1 RR00400 (to the University of Minnesota), HL58977 (to Wake Forest University), HV-48141 (to the Mammalian Genotyping Service), and HRRC 93-196 (to the University of New Mexico). We are indebted to our patients and to the families who have participated in this study. In addition to the authors, other coinvestigators and key support staff for the CSGA include the following: Johns Hopkins University—Alkis Togias, Shau Ku Huang, Linda Freidhoff, Marion Stockton, Eva Ehrlich, and Beverly Plunkett; University of Chicago—Raoul Wolf, Heidi Gidley, Rhonda Peterson, Stephanie Willadsen, Patrick Klimczyck, and Anya Tsalenko; University of Maryland (and University of New Mexico)—Shirley Murphy, Jonathon Samet, O Colin Stine, Lilly Zheng, Adam Boldt, Betsy Rechtsteiner, and Shannon Gierczak; University of Minnesota—William Oetting, Marcia Brott, Duaine Jackola, Andreas Rosenberg, Edward Corazalla, Sandra Leikam, and Lisa Daniels; and Wake Forest University (Data Coordinating Center)—June Pierce and Allison Florance. We wish to acknowledge the Observational and Safety Monitoring Board—William Busse (chair), Ellen Wijsman, and Jeffrey Chamberlain; and National Heart, Lung, and Blood Institute staff—Susan Banks-Schlegel. The Chair of the Steering Committee is rotated between the principal investigators: Carole Ober (current), Terri Beaty, Eugene Bleecker, and Malcolm Blumenthal.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1086/320589
DO - 10.1086/320589
M3 - Article
C2 - 11349227
AN - SCOPUS:0034981942
SN - 0002-9297
VL - 68
SP - 1437
EP - 1446
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -