A genome-wide search for allergic response (atopy) genes in three ethnic groups collaborative study of the genetics of asthma

Malcolm N. Blumenthal, Carl D. Langefeld, Terri H. Beaty, Eugene R. Bleecker, Carole Ober, Lucille Lester, Ethan Lange, Kathleen C. Barnes, Raoul Wolf, Richard A. King, Julian Solway, William Oetting, Deborah A. Meyers, Stephen S. Rich

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55 Scopus citations

Abstract

Atopy is an IgE-mediated condition known to aggregate in families and is a major risk factor for asthma. As part of the Collaborative Study on the Genetics of Asthma (CSGA), a genome-wide scan for atopy, defined by skin sensitivity to one or more common environmental allergens, was conducted in 287 CSGA families (115 African American, 138 Caucasian and 34 Hispanic). Using a nonparametric genetic analysis approach, two regions were observed in the sample of all families that yielded multipoint lod scores >1.5 (chromosome 11q, lod=1.55 between D11S1986 and D11S 1998; chromosome 20p between D20S473 and D20S604, lod=1.54). Modeling that included multiple genomic positions simultaneously indicated that four chromosomal regions accounted for the majority of evidence for linkage in the combined families. These four regions are on chromosomes 10p near D10S1412 (lod=0.94), 11q near D11S1986 (lod=1.76), 17q near D17S784 (lod=0.97) and 20p near D20S473 (lod=1.74). In the subset of pedigrees giving positive evidence for linkage on chromosome 11q, the evidence for linkage increased by lod scores greater than one in four other chromosomal regions: 5q (D5S1480, lod=1.65), 8p (D8S1113, lod=1.60), 12p (D12S372, lod=1.54) and 14q (D14S749, lod=1.70). These results suggest that several regions may harbor genes contributing to the risk for atopy and these may interact with one another in a complex manner.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalHuman Genetics
Volume114
Issue number2
DOIs
StatePublished - Jan 2004

Bibliographical note

Funding Information:
Acknowledgements This study was supported by the following NIH grants: U01 HL49612 (JHU), U01 HL49596 and M01 RR00055 (UC), U01 HL59609 and M01 RR00400 (UMN), U01 HL58977, U01 HL49602, U01 HL49609 and M01 RR00600 (University of Maryland and Wake Forest University), HV-48141 (Mammalian Genotyping Service), and HRRC 93-196 (University of New Mexico). In addition to the authors, other co-investigators and key support personnel for the CSGA include: Eva Ehrlich, Linda Freidhoff, Rasika Mathias, Beverly Plunkett and Maria Stockton (Johns Hopkins University), Rhonda Peterson, Jennifer Anderson and Heidi Gidley (University of Chicago), Lisa Daniels, Edward Corazalla and Marcia Brott (University of Minnesota), June Pierce, Mark Brown, Adrienne Hill and Cralen Davis (Wake Forest University Data Coordinating Center), and Tim Howard and Jianfeng Xu (Wake Forest University).

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