Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction by 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, J├Ânsson 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 in Nature genetics (2009). PubMed

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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