Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

D.F. Gudbjartsson; U.S. Bjornsdottir; E. Halapi; A. Helgadottir; P. Sulem; G.M. Jonsdottir; G. Thorleifsson; H. Helgadottir; V. Steinthorsdottir; H. Stefansson; C. Williams; J. Hui; John Beilby; Nicole Warrington; A. James; Lyle Palmer; G.H. Koppelman; A. Heinzmann; M. Krueger; H.M. Boezen; A. Wheatley; J. Altmuller; H.D. Shin; S. Uh; H.S. Cheong; B. Jonsdottir; D. Gislason; C. Park; L.M. Rasmussen; C. Porsbjerg; J.W. Hansen; V. Backer; T. Werge; C. Janson; U. Jonsson; M.C.Y. Ng; J. Chan; W.Y. So; R. Ma; S.H. Shah; C.B. Granger; A.A. Quyyumi; A.I. Levey; V. Vaccarino; M.P. Reilly; D.J. Rader; M.J.A. Williams; A.M. Van Rij; G.T. Jones; E. Trabetti; G. Malerba; P.F. Pignatti; A. Boner; L. Pescollderungg; D. Girelli; O. Olivieri; N. Martinelli; B.R. Ludviksson; D. Ludviksdottir; G.I. Eyjolfsson; D. Arnar; G. Thorgeirsson; K. Deichmann; Philip Thompson; M. Wjst; I.P. Hall; D.S. Postma; T. Gislason; J. Gulcher; A. Kong; I. Jonsdottir; U. Thorsteinsdottir; K. Stefansson

doi:10.1038/ng.323

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

D.F. Gudbjartsson, U.S. Bjornsdottir, E. Halapi, A. Helgadottir, P. Sulem, G.M. Jonsdottir, G. Thorleifsson, H. Helgadottir, V. Steinthorsdottir, H. Stefansson, C. Williams, J. Hui, John Beilby, Nicole Warrington, A. James, Lyle Palmer, G.H. Koppelman, A. Heinzmann, M. Krueger, H.M. BoezenA. Wheatley, J. Altmuller, H.D. Shin, S. Uh, H.S. Cheong, B. Jonsdottir, D. Gislason, C. Park, L.M. Rasmussen, C. Porsbjerg, J.W. Hansen, V. Backer, T. Werge, C. Janson, U. Jonsson, M.C.Y. Ng, J. Chan, W.Y. So, R. Ma, S.H. Shah, C.B. Granger, A.A. Quyyumi, A.I. Levey, V. Vaccarino, M.P. Reilly, D.J. Rader, M.J.A. Williams, A.M. Van Rij, G.T. Jones, E. Trabetti, G. Malerba, P.F. Pignatti, A. Boner, L. Pescollderungg, D. Girelli, O. Olivieri, N. Martinelli, B.R. Ludviksson, D. Ludviksdottir, G.I. Eyjolfsson, D. Arnar, G. Thorgeirsson, K. Deichmann, Philip Thompson, M. Wjst, I.P. Hall, D.S. Postma, T. Gislason, J. Gulcher, A. Kong, I. Jonsdottir, U. Thorsteinsdottir, K. Stefansson

Research output: Contribution to journal › Article

571 Citations (Scopus)

Abstract

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).

Original language	English
Pages (from-to)	342-347
Journal	Nature Genetics
Volume	41
Issue number	3
DOIs	https://doi.org/10.1038/ng.323
Publication status	Published - 2009

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Gudbjartsson, D. F., Bjornsdottir, U. S., Halapi, E., Helgadottir, A., Sulem, P., Jonsdottir, G. M., Thorleifsson, G., Helgadottir, H., Steinthorsdottir, V., Stefansson, H., Williams, C., Hui, J., Beilby, J., Warrington, N., James, A., Palmer, L., Koppelman, G. H., Heinzmann, A., Krueger, M., ... Stefansson, K. (2009). Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nature Genetics, 41(3), 342-347. https://doi.org/10.1038/ng.323

Gudbjartsson, D.F. ; Bjornsdottir, U.S. ; Halapi, E. ; Helgadottir, A. ; Sulem, P. ; Jonsdottir, G.M. ; Thorleifsson, G. ; Helgadottir, H. ; Steinthorsdottir, V. ; Stefansson, H. ; Williams, C. ; Hui, J. ; Beilby, John ; Warrington, Nicole ; James, A. ; Palmer, Lyle ; Koppelman, G.H. ; Heinzmann, A. ; Krueger, M. ; Boezen, H.M. ; Wheatley, A. ; Altmuller, J. ; Shin, H.D. ; Uh, S. ; Cheong, H.S. ; Jonsdottir, B. ; Gislason, D. ; Park, C. ; Rasmussen, L.M. ; Porsbjerg, C. ; Hansen, J.W. ; Backer, V. ; Werge, T. ; Janson, C. ; Jonsson, U. ; Ng, M.C.Y. ; Chan, J. ; So, W.Y. ; Ma, R. ; Shah, S.H. ; Granger, C.B. ; Quyyumi, A.A. ; Levey, A.I. ; Vaccarino, V. ; Reilly, M.P. ; Rader, D.J. ; Williams, M.J.A. ; Van Rij, A.M. ; Jones, G.T. ; Trabetti, E. ; Malerba, G. ; Pignatti, P.F. ; Boner, A. ; Pescollderungg, L. ; Girelli, D. ; Olivieri, O. ; Martinelli, N. ; Ludviksson, B.R. ; Ludviksdottir, D. ; Eyjolfsson, G.I. ; Arnar, D. ; Thorgeirsson, G. ; Deichmann, K. ; Thompson, Philip ; Wjst, M. ; Hall, I.P. ; Postma, D.S. ; Gislason, T. ; Gulcher, J. ; Kong, A. ; Jonsdottir, I. ; Thorsteinsdottir, U. ; Stefansson, K. / Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. In: Nature Genetics. 2009 ; Vol. 41, No. 3. pp. 342-347.

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abstract = "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).",

author = "D.F. Gudbjartsson and U.S. Bjornsdottir and E. Halapi and A. Helgadottir and P. Sulem and G.M. Jonsdottir and G. Thorleifsson and H. Helgadottir and V. Steinthorsdottir and H. Stefansson and C. Williams and J. Hui and John Beilby and Nicole Warrington and A. James and Lyle Palmer and G.H. Koppelman and A. Heinzmann and M. Krueger and H.M. Boezen and A. Wheatley and J. Altmuller and H.D. Shin and S. Uh and H.S. Cheong and B. Jonsdottir and D. Gislason and C. Park and L.M. Rasmussen and C. Porsbjerg and J.W. Hansen and V. Backer and T. Werge and C. Janson and U. Jonsson and M.C.Y. Ng and J. Chan and W.Y. So and R. Ma and S.H. Shah and C.B. Granger and A.A. Quyyumi and A.I. Levey and V. Vaccarino and M.P. Reilly and D.J. Rader and M.J.A. Williams and {Van Rij}, A.M. and G.T. Jones and E. Trabetti and G. Malerba and P.F. Pignatti and A. Boner and L. Pescollderungg and D. Girelli and O. Olivieri and N. Martinelli and B.R. Ludviksson and D. Ludviksdottir and G.I. Eyjolfsson and D. Arnar and G. Thorgeirsson and K. Deichmann and Philip Thompson and M. Wjst and I.P. Hall and D.S. Postma and T. Gislason and J. Gulcher and A. Kong and I. Jonsdottir and U. Thorsteinsdottir and K. Stefansson",

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doi = "10.1038/ng.323",

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Gudbjartsson, DF, Bjornsdottir, US, Halapi, E, Helgadottir, A, Sulem, P, Jonsdottir, GM, Thorleifsson, G, Helgadottir, H, Steinthorsdottir, V, Stefansson, H, Williams, C, Hui, J , Beilby, J, Warrington, N, James, A, Palmer, L, Koppelman, GH, Heinzmann, A, Krueger, M, Boezen, HM, Wheatley, A, Altmuller, J, Shin, HD, Uh, S, Cheong, HS, Jonsdottir, B, Gislason, D, Park, C, Rasmussen, LM, Porsbjerg, C, Hansen, JW, Backer, V, Werge, T, Janson, C, Jonsson, U, Ng, MCY, Chan, J, So, WY, Ma, R, Shah, SH, Granger, CB, Quyyumi, AA, Levey, AI, Vaccarino, V, Reilly, MP, Rader, DJ, Williams, MJA, Van Rij, AM, Jones, GT, Trabetti, E, Malerba, G, Pignatti, PF, Boner, A, Pescollderungg, L, Girelli, D, Olivieri, O, Martinelli, N, Ludviksson, BR, Ludviksdottir, D, Eyjolfsson, GI, Arnar, D, Thorgeirsson, G, Deichmann, K, Thompson, P, Wjst, M, Hall, IP, Postma, DS, Gislason, T, Gulcher, J, Kong, A, Jonsdottir, I, Thorsteinsdottir, U & Stefansson, K 2009, 'Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction', Nature Genetics, vol. 41, no. 3, pp. 342-347. https://doi.org/10.1038/ng.323

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. / Gudbjartsson, D.F.; Bjornsdottir, U.S.; Halapi, E.; Helgadottir, A.; Sulem, P.; Jonsdottir, G.M.; Thorleifsson, G.; Helgadottir, H.; Steinthorsdottir, V.; Stefansson, H.; Williams, C.; Hui, J.; Beilby, John; Warrington, Nicole; James, A.; Palmer, Lyle; Koppelman, G.H.; Heinzmann, A.; Krueger, M.; Boezen, H.M.; Wheatley, A.; Altmuller, J.; Shin, H.D.; Uh, S.; Cheong, H.S.; Jonsdottir, B.; Gislason, D.; Park, C.; Rasmussen, L.M.; Porsbjerg, C.; Hansen, J.W.; Backer, V.; Werge, T.; Janson, C.; Jonsson, U.; Ng, M.C.Y.; Chan, J.; So, W.Y.; Ma, R.; Shah, S.H.; Granger, C.B.; Quyyumi, A.A.; Levey, A.I.; Vaccarino, V.; Reilly, M.P.; Rader, D.J.; Williams, M.J.A.; Van Rij, A.M.; Jones, G.T.; Trabetti, E.; Malerba, G.; Pignatti, P.F.; Boner, A.; Pescollderungg, L.; Girelli, D.; Olivieri, O.; Martinelli, N.; Ludviksson, B.R.; Ludviksdottir, D.; Eyjolfsson, G.I.; Arnar, D.; Thorgeirsson, G.; Deichmann, K.; Thompson, Philip; Wjst, M.; Hall, I.P.; Postma, D.S.; Gislason, T.; Gulcher, J.; Kong, A.; Jonsdottir, I.; Thorsteinsdottir, U.; Stefansson, K.

In: Nature Genetics, Vol. 41, No. 3, 2009, p. 342-347.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

AU - Gudbjartsson, D.F.

AU - Bjornsdottir, U.S.

AU - Halapi, E.

AU - Helgadottir, A.

AU - Sulem, P.

AU - Jonsdottir, G.M.

AU - Thorleifsson, G.

AU - Helgadottir, H.

AU - Steinthorsdottir, V.

AU - Stefansson, H.

AU - Williams, C.

AU - Hui, J.

AU - Beilby, John

AU - Warrington, Nicole

AU - James, A.

AU - Palmer, Lyle

AU - Koppelman, G.H.

AU - Heinzmann, A.

AU - Krueger, M.

AU - Boezen, H.M.

AU - Wheatley, A.

AU - Altmuller, J.

AU - Shin, H.D.

AU - Uh, S.

AU - Cheong, H.S.

AU - Jonsdottir, B.

AU - Gislason, D.

AU - Park, C.

AU - Rasmussen, L.M.

AU - Porsbjerg, C.

AU - Hansen, J.W.

AU - Backer, V.

AU - Werge, T.

AU - Janson, C.

AU - Jonsson, U.

AU - Ng, M.C.Y.

AU - Chan, J.

AU - So, W.Y.

AU - Ma, R.

AU - Shah, S.H.

AU - Granger, C.B.

AU - Quyyumi, A.A.

AU - Levey, A.I.

AU - Vaccarino, V.

AU - Reilly, M.P.

AU - Rader, D.J.

AU - Williams, M.J.A.

AU - Van Rij, A.M.

AU - Jones, G.T.

AU - Trabetti, E.

AU - Malerba, G.

AU - Pignatti, P.F.

AU - Boner, A.

AU - Pescollderungg, L.

AU - Girelli, D.

AU - Olivieri, O.

AU - Martinelli, N.

AU - Ludviksson, B.R.

AU - Ludviksdottir, D.

AU - Eyjolfsson, G.I.

AU - Arnar, D.

AU - Thorgeirsson, G.

AU - Deichmann, K.

AU - Thompson, Philip

AU - Wjst, M.

AU - Hall, I.P.

AU - Postma, D.S.

AU - Gislason, T.

AU - Gulcher, J.

AU - Kong, A.

AU - Jonsdottir, I.

AU - Thorsteinsdottir, U.

AU - Stefansson, K.

PY - 2009

Y1 - 2009

N2 - 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).

AB - 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).

U2 - 10.1038/ng.323

DO - 10.1038/ng.323

M3 - Article

VL - 41

SP - 342

EP - 347

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

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