Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
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.
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).