A genome-wide search for asthma susceptibility loci in ethnically diverse populations

David G. Marsh, Nancy E. Maestri, Linda R. Freidhoff, Kathleen C. Barnes, Alkis Togias, Eva Ehrlich, Terri Beaty, David Duffy, Richard Rosenthal, Farhad Imani, Georgia Dunston, Paulette Furbert-Harris, Floyd Malveaux, Carole Ober, Nancy J. Cox, Lucille A. Lester, Rhonda Peterson, Heidi Gidley, Anna Pluzhnikov, Jennifer AndersonJulian Solway, Alan Leff, Raoul Wolf, Mark Wylam, Bradley Kurtz, Anthony Richardson, Rodney Parry, Malcolm N. Blumenthal, Richard A. King, William Oetting, Delores Drury, Andreas Rosenberg, Lisa Daniels, Charlene McEvoy, Jay Lou, Mark Hamra, Marcia Brott, Stephen S. Rich, Beverly J. Spray, James L. Weber, Bo Yuan, Zhenyuan Wang, Eugene R. Bleecker, Pamela Amelung, Betsy Rechstiner, Deborah A. Meyers, Jonathan Samet, Denise Wiesch, Jianfeng Xu, Shirley Murphy, Susan Banks-Schlegel

Research output: Contribution to journalArticle

640 Scopus citations

Abstract

Asthma is an inflammatory airways disease associated with intermittent respiratory symptoms, bronchial hyperresponsiveness (BHR) and reversible airflow obstruction and is phenotypically heterogeneous. Patterns of clustering and segregation analyses in asthma families have suggested a genetic component to asthma. Previous studies reported linkage of BHR and atopy to chromosomes 5q (refs 7-9), 6p (refs 10-12), 11q (refs 13-15), 14q (ref. 16), and 12q (ref. 17) using candidate gene approaches. However, the relative roles of these genes in the pathogenesis of asthma or atopy are difficult to assess outside of the context of a genome-wide search. One genome-wide search in atopic sib pairs has been reported, however, only 12% of their subjects had asthma. We conducted a genome-wide search in 140 families with ≤2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions: 5p15 (P = 0.0008) and 17p11.1- q11.2 (P=0.0015) in African Americans; 11p15 (P = 0.0089) and 19q13 (P = 0.0013) in Caucasians; 2q33 (P = 0.0005) and 21q21 (P = 0.0040) in Hispanics. Evidence for linkage was also detected in five regions previously reported to be linked to asthma-associated phenotypes: 5q23-31 (P = 0.0187), 6p21.3-23 (P = 0.0129), 12q14-24.2 (P = 0.0042), 13q21.3-qter (P = 0.0014), and 14q11.2- 13 (P = 0.0062) in Caucasians and 12q14-24.2 (P = 0.0260) in Hispanics.

Original languageEnglish (US)
Pages (from-to)389-392
Number of pages4
JournalNature Genetics
Volume15
Issue number4
DOIs
StatePublished - Apr 1 1997

ASJC Scopus subject areas

  • Genetics

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    Marsh, D. G., Maestri, N. E., Freidhoff, L. R., Barnes, K. C., Togias, A., Ehrlich, E., Beaty, T., Duffy, D., Rosenthal, R., Imani, F., Dunston, G., Furbert-Harris, P., Malveaux, F., Ober, C., Cox, N. J., Lester, L. A., Peterson, R., Gidley, H., Pluzhnikov, A., ... Banks-Schlegel, S. (1997). A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nature Genetics, 15(4), 389-392. https://doi.org/10.1038/ng0497-389