Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Dara G. Torgerson, Elizabeth J. Ampleford, Grace Y. Chiu, W. James Gauderman, Christopher R. Gignoux, Penelope E. Graves, Blanca E. Himes, Albert M. Levin, Rasika A. Mathias, Dana B. Hancock, James W. Baurley, Celeste Eng, Debra A. Stern, Juan C. Celedón, Nicholas Rafaels, Daniel Capurso, David V. Conti, Lindsey A. Roth, Manuel Soto-Quiros, Alkis TogiasXingnan Li, Rachel A. Myers, Isabelle Romieu, David J Van Den Berg, Donglei Hu, Nadia N. Hansel, Ryan D. Hernandez, Elliott Israel, Muhammad T. Salam, Joshua Galanter, Pedro C. Avila, Lydiana Avila, Jose R. Rodriquez-Santana, Rocio Chapela, William Rodriguez-Cintron, Gregory B. Diette, N. Franklin Adkinson, Rebekah A. Abel, Kevin D. Ross, Min Shi, Mezbah U. Faruque, Georgia M. Dunston, Harold R. Watson, Vito J. Mantese, Serpil C. Ezurum, Liming Liang, Ingo Ruczinski, Jean G. Ford, Scott Huntsman, Kian Fan Chung, Hita Vora, Xia Li, William Calhoun, Mario Castro, Juan J. Sienra-Monge, Blanca Del Rio-Navarro, Klaus A. Deichmann, Andrea Heinzmann, Sally E. Wenzel, William W. Busse, James E. Gern, Robert F. Lemanske, Terri H. Beaty, Eugene R. Bleecker, Benjamin A. Raby, Deborah A. Meyers, Stephanie J. London, Frank D. Gilliland, Esteban G. Burchard, Fernando D. Martinez, Scott T. Weiss, L. Keoki Williams, Kathleen C. Barnes, Carole Ober, Dan L. Nicolae

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Abstract

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10-9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Original languageEnglish (US)
Pages (from-to)887-892
Number of pages6
JournalNature Genetics
Volume43
Issue number9
DOIs
StatePublished - Sep 2011

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ASJC Scopus subject areas

  • Genetics

Cite this

Torgerson, D. G., Ampleford, E. J., Chiu, G. Y., Gauderman, W. J., Gignoux, C. R., Graves, P. E., Himes, B. E., Levin, A. M., Mathias, R. A., Hancock, D. B., Baurley, J. W., Eng, C., Stern, D. A., Celedón, J. C., Rafaels, N., Capurso, D., Conti, D. V., Roth, L. A., Soto-Quiros, M., ... Nicolae, D. L. (2011). Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nature Genetics, 43(9), 887-892. https://doi.org/10.1038/ng.888