title: Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
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).
authors.affiliation: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. daniel.gudbjartsson@decode.is
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000465:Algorithms; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D004804:Eosinophils / Q000166:cytology* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics; D020570:Genes, myb / Q000502:physiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007055:Iceland; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007958:Leukocyte Count; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D005136:Eye Proteins; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; C490778:SH2B3 protein, human; C502341:WDR36 protein, human