Abstract
Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.
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Acknowledgments
This work is supported by Contract HHSN26800625226C from the National Heart, Lung, and Blood Institute, T32 5T32HD040128-09 from the National Institutes of Health, the American Asthma Foundation, the American Medical Association Seed Grant Research Program, and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating the CARe resource for biomedical research. The following studies, funded by the listed National Institutes of Health grants, were utilized in this study. Atherosclerosis Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015, N01-HC-55018), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022). Coronary Artery Risk in Young Adults: University of Alabama at Birmingham (N01-HC-48047, N01-HC- 95095), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), Tufts-New England Medical Center (N01-HC- 45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Jackson Heart Study: Contracts N01-HC-95170, N01-HC-95171, N01-HC-95172 from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities, with additional support from the National Institute on Biomedical Imaging and Bioengineering. Multi-Ethnic Study of Atherosclerosis: University of Washington (N01-HC-95159), University of California, Los Angeles (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205). Pulmonary phenotyping and analyses in MESA are funded by NIH grants R01-HL077612, RC1-HL100543 and R01-HL093081.
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D. B. Kantor and C. D. Palmer contributed equally to this work.
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Kantor, D.B., Palmer, C.D., Young, T.R. et al. Replication and fine mapping of asthma-associated loci in individuals of African ancestry. Hum Genet 132, 1039–1047 (2013). https://doi.org/10.1007/s00439-013-1310-7
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DOI: https://doi.org/10.1007/s00439-013-1310-7