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Replication and fine mapping of asthma-associated loci in individuals of African ancestry |
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| Authors: | David B Kantor Cameron D Palmer Taylor R Young Yan Meng Zofia K Gajdos Helen Lyon Alkes L Price Samuela Pollack Stephanie J London Laura R Loehr Lewis J Smith Rajesh Kumar David R Jacobs Jr Marcy F Petrini George T O’Connor Wendy B White George Papanicolaou Kristin M Burkart Susan R Heckbert R Graham Barr Joel N Hirschhorn |
| Institution: | 1. Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA 2. Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA, 02142, USA 3. Departments of Epidemiology and Biostatistics, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA 4. Division of Intramural Research, DHHS, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC, 27709, USA 5. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, 27599, USA 6. Northwestern University, Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, 240 E. Huron Ave, Chicago, IL, 60611, USA 7. Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E Chicago Avenue, Chicago, IL, 60611, USA 8. Division of Epidemiology and Community Health, University of Minnesota, 1300 S. 2nd Street Suite 300, Minneapolis, MN, 55454, USA 9. Division of Pulmonary, Critical Care and Sleep Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216-4505, USA 10. Department of Medicine, Pulmonary Center, Boston University School of Medicine, Room R 304, 72. E. Concord St, Boston, MA, 02118, USA 11. Tougaloo College and Jackson Heart Study, 500 West County Line Road, Tougaloo, MS, 39174, USA 12. Division of Prevention and Population Sciences, National Heart, Lung and Blood Institute, National Institutes of Health, Two Rockledge Center, Suite 10018 6701 Rockledge Drive, MSC 7936, Bethesda, MD, 20892-7936, USA 13. Division of Pulmonary, Allergy and Critical Care, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, PH 8 East, Room 101, New York, NY, 10032, USA 14. University of Washington, Department of Epidemiology, School of Public Health, Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA, 98101-1466, USA 15. Department of Medicine, College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health, Columbia University, PH 9 East, Room 105, New York, NY, 10032, USA 16. Division of Endocrinology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA 17. Departments of Genetics and Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA |
| 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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