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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction


Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 × 10−14, 5.4 × 10−10, 8.6 × 10−17, 1.2 × 10−10 and 6.5 × 10−19, respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 × 10−12) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 × 10−6, 2.2 × 10−5 and 2.4 × 10−4, respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 × 10−8) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

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Figure 1
Figure 2: Association of SNPs identified through the blood eosinophil count genome-wide scan with differential white blood cell counts, platelet counts and red blood.

Accession codes




  1. 1

    Hogan, S.P. et al. Eosinophils: biological properties and role in health and disease. Clin. Exp. Allergy 38, 709–750 (2008).

    CAS  Article  Google Scholar 

  2. 2

    Lee, J.J. et al. Defining a link with asthma in mice congenitally deficient in eosinophils. Science 305, 1773–1776 (2004).

    CAS  Article  Google Scholar 

  3. 3

    International Hap Map Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

  4. 4

    Schmitz, J. et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23, 479–490 (2005).

    CAS  Article  Google Scholar 

  5. 5

    Carriere, V. et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc. Natl. Acad. Sci. USA 104, 282–287 (2007).

    CAS  Article  Google Scholar 

  6. 6

    Cherry, W.B., Yoon, J., Bartemes, K.R., Iijima, K. & Kita, H. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils. J. Allergy Clin. Immunol. 121, 1484–1490 (2008).

    CAS  Article  Google Scholar 

  7. 7

    Zhernakova, A. et al. Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am. J. Hum. Genet. 82, 1202–1210 (2008).

    CAS  Article  Google Scholar 

  8. 8

    Hunt, K.A. et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet. 40, 395–402 (2008).

    CAS  Article  Google Scholar 

  9. 9

    Shimizu, M. et al. Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Hum. Mol. Genet. 14, 2919–2927 (2005).

    CAS  Article  Google Scholar 

  10. 10

    Zhu, G. et al. Interleukin 18 receptor 1 gene polymorphisms are associated with asthma. Eur. J. Hum. Genet. 16, 1083–1090 (2008).

    CAS  Article  Google Scholar 

  11. 11

    Reijmerink, N.E. et al. Association of IL1RL1, IL18R1, and IL18RAP gene cluster polymorphisms with asthma and atopy. J. Allergy Clin. Immunol. 122, 651–654 (2008).

    Article  Google Scholar 

  12. 12

    Mao, M. et al. T lymphocyte activation gene identification by coregulated expression on DNA microarrays. Genomics 83, 989–999 (2004).

    CAS  Article  Google Scholar 

  13. 13

    Zhou, B. et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat. Immunol. 6, 1047–1053 (2005).

    CAS  Article  Google Scholar 

  14. 14

    Ying, S. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174, 8183–8190 (2005).

    CAS  Article  Google Scholar 

  15. 15

    Thein, S.L. et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc. Natl. Acad. Sci. USA 104, 11346–11351 (2007).

    CAS  Article  Google Scholar 

  16. 16

    Menzel, S. et al. The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans. Blood 110, 3624–3626 (2007).

    CAS  Article  Google Scholar 

  17. 17

    Martinez-Moczygemba, M. & Huston, D.P. Biology of common β receptor-signaling cytokines: IL-3, IL-5, and GM-CSF. J. Allergy Clin. Immunol. 112, 653–665 (2003).

    CAS  Article  Google Scholar 

  18. 18

    Thorgeirsson, T.E. et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452, 638–642 (2008).

    CAS  Article  Google Scholar 

  19. 19

    Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

  20. 20

    Todd, J.A. et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 39, 857–864 (2007).

    CAS  Article  Google Scholar 

  21. 21

    Velazquez, L. et al. Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice. J. Exp. Med. 195, 1599–1611 (2002).

    CAS  Article  Google Scholar 

  22. 22

    Hirasawa, R. et al. Essential and instructive roles of GATA factors in eosinophil development. J. Exp. Med. 195, 1379–1386 (2002).

    CAS  Article  Google Scholar 

  23. 23

    Iwasaki, H. et al. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev. 20, 3010–3021 (2006).

    CAS  Article  Google Scholar 

  24. 24

    Rebollo, A. & Schmitt, C. Ikaros, Aiolos and Helios: transcription regulators and lymphoid malignancies. Immunol. Cell Biol. 81, 171–175 (2003).

    CAS  Article  Google Scholar 

  25. 25

    Gudbjartsson, D.F. et al. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat. Genet. 40, 886–891 (2008).

    CAS  Article  Google Scholar 

  26. 26

    Vitart, V. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat. Genet. 40, 437–442 (2008).

    CAS  Article  Google Scholar 

  27. 27

    Devlin, B., Bacanu, S.A. & Roeder, K. Genomic Control to the extreme. Nat. Genet. 36, 1129–1130 (2004).

    CAS  Article  Google Scholar 

  28. 28

    Gretarsdottir, S. et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat. Genet. 35, 131–138 (2003).

    CAS  Article  Google Scholar 

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The genotyping of some of the myocardial infarction sample sets was funded in part through a grant from the US National Heart, Lung, and Blood Institute (SR01HL089650-01). The New Zealand cohort study was supported by a programme grant from the Health Research Council of New Zealand. The Korean study was supported by a grant from the Korean Health 21 R&D project, Ministry of Health & Welfare, Republic of Korea (A010249).

Author information




D.F.G., U.S.B., M.W., I.P.H., D.S.P., I.J., U.T. and K.S. wrote the first draft of the paper. U.S.B., E.H., A. Helgadottir, B.J., D. Gislason, B.R.L., D.L., G.I.E., D.A. and G. Thorgeirsson participated in the collection of the Icelandic data. C.W., J.H., J.B., N.M.W., A.J., L.J.P. and P.J.T. collected the Australian data. G.H.K., H.M.B. and D.S.P. collected the Dutch data. A. Heinzmann, M.K., J.A.,K.D. and M.W. collected the German data. A.W. and I.P.H. collected the UK data. H.D.S., S.-T.U., H.S.C. and C.-S.P. collected the Korean data. L.M.R., C.P., J.W.H., V.B. and T.W. collected the Danish data. C.J. and U.-B.J. collected the Swedish data. M.C.Y.N., J.C., W.Y.S. and R.M. collected the Hong Kong data. S.H.S., C.B.G, A.A.Q., A.I.L., V.V., M.P.R. and D.J.R. collected the US data. M.J.A.W., A.M.V.R. and G.T.J. collected the New Zealand data. E.T., G.M., P.F.P., A.B., L.P., D. Girelli, O.O. and N.M. collected the Italian data. E.H., A. Helgadottir, H.H., V.S. and U.T. carried out the genotyping. D.F.G., P.S., G.M.J., G. Thorleifsson, H.S. and A.K. analyzed the data. D.F.G., U.S.B., K.D., P.J.T., M.W., I.P.H., D.S.P., T.G., J.G., I.J., U.T. and K.S. planned and supervised the work. All authors contributed to the final version of the paper.

Corresponding authors

Correspondence to Daniel F Gudbjartsson or Kari Stefansson.

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Supplementary Methods, Supplementary Tables 1–7 and Supplementary Figures 1–3 (PDF 2110 kb)

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Gudbjartsson, D., Bjornsdottir, U., Halapi, E. et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 41, 342–347 (2009).

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