Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
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).
Gudbjartsson
Daniel F
DF
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. daniel.gudbjartsson@decode.is
Bjornsdottir
Unnur S
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Halapi
Eva
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Helgadottir
Anna
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Sulem
Patrick
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Jonsdottir
Gudrun M
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Thorleifsson
Gudmar
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Helgadottir
Hafdis
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Steinthorsdottir
Valgerdur
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Stefansson
Hreinn
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Williams
Carolyn
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Hui
Jennie
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Beilby
John
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Warrington
Nicole M
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James
Alan
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Palmer
Lyle J
LJ
Koppelman
Gerard H
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Heinzmann
Andrea
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Krueger
Marcus
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Boezen
H Marike
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Wheatley
Amanda
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Altmuller
Janine
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Shin
Hyoung Doo
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Soo-Taek
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Cheong
Hyun Sub
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Jonsdottir
Brynja
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Gislason
David
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Park
Choon-Sik
CS
Rasmussen
Linda M
LM
Porsbjerg
Celeste
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Hansen
Jakob W
JW
Backer
Vibeke
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Werge
Thomas
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Janson
Christer
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Jönsson
Ulla-Britt
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Ng
Maggie C Y
MC
Chan
Juliana
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So
Wing Yee
WY
Ma
Ronald
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Shah
Svati H
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Granger
Christopher B
CB
Quyyumi
Arshed A
AA
Levey
Allan I
AI
Vaccarino
Viola
V
Reilly
Muredach P
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Rader
Daniel J
DJ
Williams
Michael J A
MJ
van Rij
Andre M
AM
Jones
Gregory T
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Trabetti
Elisabetta
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Malerba
Giovanni
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Pignatti
Pier Franco
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Boner
Attilio
A
Pescollderungg
Lydia
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Girelli
Domenico
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Olivieri
Oliviero
O
Martinelli
Nicola
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Ludviksson
Bjorn R
BR
Ludviksdottir
Dora
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Eyjolfsson
Gudmundur I
GI
Arnar
David
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Thorgeirsson
Gudmundur
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Deichmann
Klaus
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Thompson
Philip J
PJ
Wjst
Matthias
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Hall
Ian P
IP
Postma
Dirkje S
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Gislason
Thorarinn
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Gulcher
Jeffrey
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Kong
Augustine
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Jonsdottir
Ingileif
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Thorsteinsdottir
Unnur
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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
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