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


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.

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Figure 1: Results of the meta-analysis on the chromosome 1 region of association in African Americans and African Caribbeans.


  1. 1

    Masoli, M., Fabian, D., Holt, S. & Beasley, R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59, 469–478 (2004).

    Article  Google Scholar 

  2. 2

    Moorman, J.E. et al. National surveillance for asthma–United States, 1980–2004. MMWR Surveill. Summ. 56, 1–54 (2007).

    PubMed  Google Scholar 

  3. 3

    Duffy, D.L., Martin, N.G., Battistutta, D., Hopper, J.L. & Mathews, J.D. Genetics of asthma and hay fever in Australian twins. Am. Rev. Respir. Dis. 142, 1351–1358 (1990).

    CAS  Article  Google Scholar 

  4. 4

    Nieminen, M.M., Kaprio, J. & Koskenvuo, M. A population-based study of bronchial asthma in adult twin pairs. Chest 100, 70–75 (1991).

    CAS  Article  Google Scholar 

  5. 5

    Ober, C. & Hoffjan, S. Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun. 7, 95–100 (2006).

    CAS  Article  Google Scholar 

  6. 6

    Vercelli, D. Discovering susceptibility genes for asthma and allergy. Nat. Rev. Immunol. 8, 169–182 (2008).

    CAS  Article  Google Scholar 

  7. 7

    Moffatt, M.F. et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470–473 (2007).

    CAS  Article  Google Scholar 

  8. 8

    Himes, B.E. et al. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am. J. Hum. Genet. 84, 581–593 (2009).

    CAS  Article  Google Scholar 

  9. 9

    Li, X. et al. Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J. Allergy Clin. Immunol. 125, 328–335 e11 (2010).

    CAS  Article  Google Scholar 

  10. 10

    Sleiman, P.M. et al. Variants of DENND1B associated with asthma in children. N. Engl. J. Med. 362, 36–44 (2010).

    CAS  Article  Google Scholar 

  11. 11

    Hancock, D.B. et al. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in Mexican children. PLoS Genet. 5, e1000623 (2009).

    Article  Google Scholar 

  12. 12

    Choudhry, S. et al. Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region. Hum. Genet. 123, 455–468 (2008).

    Article  Google Scholar 

  13. 13

    Mathias, R.A. et al. A genome-wide association study on African-ancestry populations for asthma. J. Allergy Clin. Immunol. 125, 336–346 e4 (2010).

    CAS  Article  Google Scholar 

  14. 14

    Bouzigon, E. et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N. Engl. J. Med. 359, 1985–1994 (2008).

    CAS  Article  Google Scholar 

  15. 15

    Galanter, J. et al. ORMDL3 gene is associated with asthma in three ethnically diverse populations. Am. J. Respir. Crit. Care Med. 177, 1194–1200 (2008).

    CAS  Article  Google Scholar 

  16. 16

    Halapi, E. et al. A sequence variant on 17q21 is associated with age at onset and severity of asthma. Eur. J. Hum. Genet. 18, 902–908 (2010).

    CAS  Article  Google Scholar 

  17. 17

    Leung, T.F. et al. Asthma and atopy are associated with chromosome 17q21 markers in Chinese children. Allergy 64, 621–628 (2009).

    CAS  Article  Google Scholar 

  18. 18

    Madore, A.M., Tremblay, K., Hudson, T.J. & Laprise, C. Replication of an association between 17q21 SNPs and asthma in a French-Canadian familial collection. Hum. Genet. 123, 93–95 (2008).

    CAS  Article  Google Scholar 

  19. 19

    Sleiman, P.M. et al. ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry. J. Allergy Clin. Immunol. 122, 1225–1227 (2008).

    CAS  Article  Google Scholar 

  20. 20

    Tavendale, R., Macgregor, D.F., Mukhopadhyay, S. & Palmer, C.N. A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J. Allergy Clin. Immunol. 121, 860–863 (2008).

    CAS  Article  Google Scholar 

  21. 21

    Wu, H. et al. Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy 64, 629–635 (2009).

    CAS  Article  Google Scholar 

  22. 22

    Bisgaard, H. et al. Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood. Am. J. Respir. Crit. Care Med. 179, 179–185 (2009).

    CAS  Article  Google Scholar 

  23. 23

    Moffatt, M.F. et al. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med. 363, 1211–1221 (2010).

    CAS  Article  Google Scholar 

  24. 24

    Choubey, D. et al. Interferon-inducible p200-family proteins as novel sensors of cytoplasmic DNA: role in inflammation and autoimmunity. J. Interferon Cytokine Res. 30, 371–380 (2010).

    CAS  Article  Google Scholar 

  25. 25

    Li, Y., Willer, C.J., Ding, J., Scheet, P. & Abecasis, G.R. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet. Epidemiol. 34, 816–834 (2010).

    Article  Google Scholar 

  26. 26

    Howie, B.N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).

    Article  Google Scholar 

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This work was supported by grants from the Office of the Director, NIH to C.O. and D.L.N. and the National Heart, Lung, and Blood Institute (HL101651 to C.O. and D.L.N.; HL087665 to D.L.N.; HL070831, HL072414 and HL049596 to C.O.; HL064307 and HL064313 to F.D.M.; HL075419, HL65899, HL083069, HL066289, HL087680, HL101543 and HL101651 to S.T.W.; HL079055 to L.K.W.; HL087699, HL49612, HL075417, HL04266 and HL072433 to K.C.B.; HL061768 and HL076647 to F.D.G.; HL087680 to W.J.G.; HL078885 and HL088133 to E.G.B.; HL87665 to D.A.M.; and HL69116, HL69130, HL69149, HL69155, HL69167, HL69170, HL69174 and HL69349 to D.A.M., E.R.B., W.W.B., W.J.C., M.C., K.F.C., S.C.E., E.I. and S.E.W.), the National Institutes of Allergy and Infectious Disease (AI070503 to C.O.; AI079139 and AI061774 to L.K.W.; AI50024, AI44840 and AI41040 to K.C.B.; and AI077439 to E.G.B.), the National Institute of Diabetes and Digestive and Kidney Diseases to L.K.W. (DK064695); the National Institutes of Environmental Health Sciences (ES09606, ES018176 and ES015903 to K.C.B.; ES007048, ES009581, R826708, RD831861 and ES011627 to F.D.G.; ES015794 to E.G.B.; and the Division of Intramural Research, Z01 ES049019, to S.J.L.); the National Center for Research Resources (RR03048 to K.C.B.), the Environmental Protection Agency (83213901 and R-826724 to K.C.B.), the American Asthma Foundation and the Fund for Henry Ford Hospital (to L.K.W.), Mary Beryl Patch Turnbull Scholar Program (to K.C.B.), the National Council of Science and Technology (Mexico) (26206-M to I. Ruczinski), the Centers for Disease Control, US (to I. Ruczinski), the Eudowood Foundation (to N.N.H.); and the Flight Attendant Medical Research Institute (FAMRI), Robert Wood Johnson Foundation (RWJF) Amos Medical Faculty Development Award, the American Asthma Foundation, and the Sandler Foundation (to E.G.B.).

The authors gratefully acknowledge the contributions of H. Moreno-Macias, A. Barraza-Villarreal and M. Ramirez-Aguilar to the MCCAS; R. McConnell, D.C. Thomas, E. Avol, K. Berhane, J. Liu, E. Rappaport and C. Edlund to the CHS; L.N. Borrell, H. Farber, R. Kumar and D. Serebrisky to the GALA and GALA2 studies; S. Thyne to the GALA2 and SAGE studies; M. LeNoir, K. Meade and H. Geoff Watson to the SAGE study; and A.V. Grant, L. Gao, C. Vergara, Y.J. Tsai, P. Gao, M.C. Liu, P. Breysse, M.B. Bracken, J. Hoh, E.W. Pugh, A.F. Scott, G. Abecasis, T. Murray, T. Hand, M. Yang, M. Campbell, C. Foster, J.B. Hetmanski, R. Ashworth, C.M. Ongaco, K.N. Hetrick and K.F. Doheny to the GRAAD study. The authors also acknowledge the support from J. Kiley, S. Banks-Schlegel and W. Gan at the National Heart, Lung, and Blood Institute and all the subjects and families that participated in these studies.

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E.R.B., B.A.R., D.A.M., S.J.L., F.D.G., W.J.G., E.G.B., F.D.M., S.T.W., L.K.W., K.C.B., C.O. and D.L.N. conceived and designed the experiments. W.J.G., A.M.L., C.E., D.J.V.D.B., M.T.S., K.D.R., E.R.B., D.A.M., S.T.W., E.G.B. and L.K.W. performed the experiments. D.G.T., E.J.A., G.Y.C., W.J.G., C.R.G., B.E.H., A.M.L., R.A. Mathias, D.B.H., J.W.B., D.A.S., N.R., D.C., D.V.C., L.A.R., Xingnan L., D.H., R.D.H., J.G., M.S., V.J.M., L.L., I. Ruczinski, S.H., H.V., Xia L., T.H.B., E.R.B., D.A.M. and D.L.N. performed statistical analysis. D.G.T., E.J.A., G.Y.C., W.J.G., C.R.G., B.E.H., A.M.L., R.A. Mathias, D.B.H., J.W.B., C.E., D.A.S., N.R., D.C., D.V.C., L.A.R., Xingnan L., R.A. Myers, D.H., M.T.S., J.G., V.J.M., L.L., I. Romieu, S.H., H.V., Xia L., T.H.B., E.R.B., D.A.M., F.D.G., L.K.W., K.C.B. and D.L.N. analyzed the data. P.E.G., A.M.L., J.C.C., D.V.C., M.S.-Q., A.T., I. Romieu, N.N.H., E.I., M.T.S., J.G., P.C.A., L.A., J.R.R.-S., R.C., W.R.-C., G.B.D., N.F.A., M.S., M.U.F., G.M.D., H.R.W., S.C.E., J.G.F., K.F.C., W.J.C., M.C., J.-J.S.-M., B.d.R.-N., K.A.D., A.H., S.E.W., W.W.B., J.E.G., R.F.L., E.R.B., D.A.M., S.J.L., F.D.G., F.D.M., S.T.W., L.K.W., E.G.B., K.C.B. and C.O. contributed reagents, materials and analysis tools. D.G.T., G.Y.C., W.J.G., B.E.H., A.M.L., R.A. Mathias, D.B.H., E.R.B., B.A.R., D.A.M., S.J.L., F.D.G., E.G.B., F.D.M., S.T.W., L.K.W., K.C.B., C.O. and D.L.N. wrote the paper. R.A.A. coordinated the study.

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Correspondence to Dan L Nicolae.

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Supplementary Figures 1–16, Supplementary Tables 1–8 and Supplementary Note. (PDF 4161 kb)

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Mexico City Childhood Asthma Study (MCAAS)., Children's Health Study (CHS) and HARBORS study., Genetics of Asthma in Latino Americans (GALA) Study, the Study of Genes-Environment and Admixture in Latino Americans (GALA2) and the Study of African Americans, Asthma, Genes & Environments (SAGE). et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43, 887–892 (2011).

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