Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Daniel F Gudbjartsson; Unnur S Bjornsdottir; Eva Halapi; Anna Helgadottir; Patrick Sulem; Gudrun M Jonsdottir; Gudmar Thorleifsson; Hafdis Helgadottir; Valgerdur Steinthorsdottir; Hreinn Stefansson; Carolyn Williams; Jennie Hui; John Beilby; Nicole M Warrington; Alan James; Lyle J Palmer; Gerard H Koppelman; Andrea Heinzmann; Marcus Krueger; H Marike Boezen; Amanda Wheatley; Janine Altmuller; Hyoung Doo Shin; Soo-Taek Uh; Hyun Sub Cheong; Brynja Jonsdottir; David Gislason; Choon-Sik Park; Linda M Rasmussen; Celeste Porsbjerg; Jakob W Hansen; Vibeke Backer; Thomas Werge; Christer Janson; Ulla-Britt Jönsson; Maggie C Y Ng; Juliana Chan; Wing Yee So; Ronald Ma; Svati H Shah; Christopher B Granger; Arshed A Quyyumi; Allan I Levey; Viola Vaccarino; Muredach P Reilly; Daniel J Rader; Michael J A Williams; Andre M van Rij; Gregory T Jones; Elisabetta Trabetti; Giovanni Malerba; Pier Franco Pignatti; Attilio Boner; Lydia Pescollderungg; Domenico Girelli; Oliviero Olivieri; Nicola Martinelli; Bjorn R Ludviksson; Dora Ludviksdottir; Gudmundur I Eyjolfsson; David Arnar; Gudmundur Thorgeirsson; Klaus Deichmann; Philip J Thompson; Matthias Wjst; Ian P Hall; Dirkje S Postma; Thorarinn Gislason; Jeffrey Gulcher; Augustine Kong; Ingileif Jonsdottir; Unnur Thorsteinsdottir; Kari Stefansson

doi:10.1038/ng.323

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Daniel F Gudbjartsson, Unnur S Bjornsdottir, Eva Halapi, Anna Helgadottir, Patrick Sulem, Gudrun M Jonsdottir, Gudmar Thorleifsson, Hafdis Helgadottir, Valgerdur Steinthorsdottir, Hreinn Stefansson, Carolyn Williams, Jennie Hui, John Beilby, Nicole M Warrington, Alan James, Lyle J Palmer, Gerard H Koppelman, Andrea Heinzmann, Marcus Krueger, H Marike BoezenAmanda Wheatley, Janine Altmuller, Hyoung Doo Shin, Soo-Taek Uh, Hyun Sub Cheong, Brynja Jonsdottir, David Gislason, Choon-Sik Park, Linda M Rasmussen, Celeste Porsbjerg, Jakob W Hansen, Vibeke Backer, Thomas Werge, Christer Janson, Ulla-Britt Jönsson, Maggie C Y Ng, Juliana Chan, Wing Yee So, Ronald Ma, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Allan I Levey, Viola Vaccarino, Muredach P Reilly, Daniel J Rader, Michael J A Williams, Andre M van Rij, Gregory T Jones, Elisabetta Trabetti, Giovanni Malerba, Pier Franco Pignatti, Attilio Boner, Lydia Pescollderungg, Domenico Girelli, Oliviero Olivieri, Nicola Martinelli, Bjorn R Ludviksson, Dora Ludviksdottir, Gudmundur I Eyjolfsson, David Arnar, Gudmundur Thorgeirsson, Klaus Deichmann, Philip J Thompson, Matthias Wjst, Ian P Hall, Dirkje S Postma, Thorarinn Gislason, Jeffrey Gulcher, Augustine Kong, Ingileif Jonsdottir, Unnur Thorsteinsdottir, Kari Stefansson

Institut for Klinisk Medicin

570 Citationer (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 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 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 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	41
Udgave nummer	3
Sider (fra-til)	342-7
Antal sider	6
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.323
Status	Udgivet - mar. 2009

Emneord

Adaptor Proteins, Vesicular Transport
Algorithms
Asthma
Case-Control Studies
Eosinophils
Eye Proteins
Genes, myb
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Iceland
Interleukins
Leukocyte Count
Myocardial Infarction
Polymorphism, Single Nucleotide
Proteins
Receptors, Cell Surface

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10.1038/ng.323

Citationsformater

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. M., James, A., Palmer, L. J., 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), 342-7. https://doi.org/10.1038/ng.323

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, NM, James, A, Palmer, LJ, Koppelman, GH, Heinzmann, A, Krueger, M, Boezen, HM, Wheatley, A, Altmuller, J, Shin, HD, Uh, S-T, Cheong, HS, Jonsdottir, B, Gislason, D, Park, C-S, Rasmussen, LM, Porsbjerg, C , Hansen, JW , Backer, V , Werge, T, Janson, C, Jönsson, U-B, 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, PJ, 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, bind 41, nr. 3, s. 342-7. https://doi.org/10.1038/ng.323

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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 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 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 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).",

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doi = "10.1038/ng.323",

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

AU - Gudbjartsson, Daniel F

AU - Bjornsdottir, Unnur S

AU - Halapi, Eva

AU - Helgadottir, Anna

AU - Sulem, Patrick

AU - Jonsdottir, Gudrun M

AU - Thorleifsson, Gudmar

AU - Helgadottir, Hafdis

AU - Steinthorsdottir, Valgerdur

AU - Stefansson, Hreinn

AU - Williams, Carolyn

AU - Hui, Jennie

AU - Beilby, John

AU - Warrington, Nicole M

AU - James, Alan

AU - Palmer, Lyle J

AU - Koppelman, Gerard H

AU - Heinzmann, Andrea

AU - Krueger, Marcus

AU - Boezen, H Marike

AU - Wheatley, Amanda

AU - Altmuller, Janine

AU - Shin, Hyoung Doo

AU - Uh, Soo-Taek

AU - Cheong, Hyun Sub

AU - Jonsdottir, Brynja

AU - Gislason, David

AU - Park, Choon-Sik

AU - Rasmussen, Linda M

AU - Porsbjerg, Celeste

AU - Hansen, Jakob W

AU - Backer, Vibeke

AU - Werge, Thomas

AU - Janson, Christer

AU - Jönsson, Ulla-Britt

AU - Ng, Maggie C Y

AU - Chan, Juliana

AU - So, Wing Yee

AU - Ma, Ronald

AU - Shah, Svati H

AU - Granger, Christopher B

AU - Quyyumi, Arshed A

AU - Levey, Allan I

AU - Vaccarino, Viola

AU - Reilly, Muredach P

AU - Rader, Daniel J

AU - Williams, Michael J A

AU - van Rij, Andre M

AU - Jones, Gregory T

AU - Trabetti, Elisabetta

AU - Malerba, Giovanni

AU - Pignatti, Pier Franco

AU - Boner, Attilio

AU - Pescollderungg, Lydia

AU - Girelli, Domenico

AU - Olivieri, Oliviero

AU - Martinelli, Nicola

AU - Ludviksson, Bjorn R

AU - Ludviksdottir, Dora

AU - Eyjolfsson, Gudmundur I

AU - Arnar, David

AU - Thorgeirsson, Gudmundur

AU - Deichmann, Klaus

AU - Thompson, Philip J

AU - Wjst, Matthias

AU - Hall, Ian P

AU - Postma, Dirkje S

AU - Gislason, Thorarinn

AU - Gulcher, Jeffrey

AU - Kong, Augustine

AU - Jonsdottir, Ingileif

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

PY - 2009/3

Y1 - 2009/3

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 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 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 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 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 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 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 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

KW - Adaptor Proteins, Vesicular Transport

KW - Algorithms

KW - Asthma

KW - Case-Control Studies

KW - Eosinophils

KW - Eye Proteins

KW - Genes, myb

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Iceland

KW - Interleukins

KW - Leukocyte Count

KW - Myocardial Infarction

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Receptors, Cell Surface

U2 - 10.1038/ng.323

DO - 10.1038/ng.323

M3 - Journal article

C2 - 19198610

SN - 1061-4036

VL - 41

SP - 342

EP - 347

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Abstract

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