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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

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Authors
Gudbjartsson, Daniel F
Bjornsdottir, Unnur S
Halapi, Eva
Helgadottir, Anna
Sulem, Patrick
Jonsdottir, Gudrun M
Thorleifsson, Gudmar
Helgadottir, Hafdis
Steinthorsdottir, Valgerdur
Stefansson, Hreinn
Williams, Carolyn
Hui, Jennie
Beilby, John
Warrington, Nicole M
James, Alan
Palmer, Lyle J
Koppelman, Gerard H
Heinzmann, Andrea
Krueger, Marcus
Boezen, H Marike
Wheatley, Amanda
Altmuller, Janine
Shin, Hyoung Doo
Uh, Soo-Taek
Cheong, Hyun Sub
Jonsdottir, Brynja
Gislason, David
Park, Choon-Sik
Rasmussen, Linda M
Porsbjerg, Celeste
Hansen, Jakob W
Backer, Vibeke
Werge, Thomas
Janson, Christer
Jönsson, Ulla-Britt
Ng, Maggie C Y
Chan, Juliana
So, Wing Yee
Ma, Ronald
Shah, Svati H
Granger, Christopher B
Quyyumi, Arshed A
Levey, Allan I
Vaccarino, Viola
Reilly, Muredach P
Rader, Daniel J
Williams, Michael J A
van Rij, Andre M
Jones, Gregory T
Trabetti, Elisabetta
Malerba, Giovanni
Pignatti, Pier Franco
Boner, Attilio
Pescollderungg, Lydia
Girelli, Domenico
Olivieri, Oliviero
Martinelli, Nicola
Ludviksson, Bjorn R
Ludviksdottir, Dora
Eyjolfsson, Gudmundur I
Arnar, David
Thorgeirsson, Gudmundur
Deichmann, Klaus
Thompson, Philip J
Wjst, Matthias
Hall, Ian P
Postma, Dirkje S
Gislason, Thorarinn
Gulcher, Jeffrey
Kong, Augustine
Jonsdottir, Ingileif
Thorsteinsdottir, Unnur
Stefansson, Kari
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Issue Date
2009-03

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Citation
Nat. Genet. 2009, 41 (3):342-7
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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http://dx.doi.org/10.1038/ng.323
ae974a485f413a2113503eed53cd6c53
10.1038/ng.323
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