Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

被引：602

作者：

Gudbjartsson, Daniel F. ^{[1
]}

Bjornsdottir, Unnur S. ^{[1
,2
]}

Halapi, Eva ^{[1
]}

Helgadottir, Anna ^{[1
]}

Sulem, Patrick ^{[1
]}

Jonsdottir, Gudrun M. ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Helgadottir, Hafdis ^{[1
]}

Steinthorsdottir, Valgerdur ^{[1
]}

Stefansson, Hreinn ^{[1
]}

Williams, Carolyn ^{[3
,4
,5
]}

Hui, Jennie ^{[6
,7
]}

Beilby, John ^{[6
,8
]}

Warrington, Nicole M. ^{[9
]}

James, Alan ^{[10
,11
]}

Palmer, Lyle J. ^{[9
]}

Koppelman, Gerard H. ^{[12
]}

Heinzmann, Andrea ^{[13
]}

Krueger, Marcus ^{[13
]}

Boezen, H. Marike ^{[14
]}

Wheatley, Amanda ^{[15
]}

Altmuller, Janine ^{[16
]}

Shin, Hyoung Doo ^{[17
,18
]}

Uh, Soo-Taek ^{[19
]}

Cheong, Hyun Sub ^{[19
]}

Jonsdottir, Brynja ^{[20
]}

Gislason, David ^{[20
]}

Park, Choon-Sik ^{[21
]}

Rasmussen, Linda M. ^{[22
]}

Porsbjerg, Celeste ^{[22
]}

Hansen, Jakob W. ^{[22
]}

Backer, Vibeke ^{[22
]}

Werge, Thomas ^{[23
]}

Janson, Christer ^{[24
]}

Joensson, Ulla-Britt ^{[24
]}

Ng, Maggie C. Y. ^{[25
]}

Chan, Juliana ^{[25
]}

So, Wing Yee ^{[25
]}

Ma, Ronald ^{[25
]}

Shah, Svati H. ^{[26
]}

Granger, Christopher B. ^{[26
]}

Quyyumi, Arshed A. ^{[27
]}

Levey, Allan I. ^{[27
]}

Vaccarino, Viola ^{[27
]}

Reilly, Muredach P. ^{[28
]}

Rader, Daniel J. ^{[28
]}

Williams, Michael J. A. ^{[29
]}

van Rij, Andre M. ^{[29
]}

Jones, Gregory T. ^{[29
]}

Trabetti, Elisabetta ^{[30
]}

机构：

[1] DeCODE Genet, IS-101 Reykjavik, Iceland

[2] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[3] Lung Inst Western Australia, Nedlands, WA 6006, Australia

[4] Western Australian Inst Med Res, Perth, WA 6000, Australia

[5] Univ Western Australia, Ctr Asthma Allergy & Resp Res, Perth, WA 6009, Australia

[6] QEII Med Ctr, PathWest Lab Med Western Australia, Dept Mol Genet, Nedlands, WA 6009, Australia

[7] Univ Western Australia, QEII Med Ctr, Western Australian Inst Med Res, Nedlands, WA 6009, Australia

[8] Univ Western Australia, Sch Surg & Pathol, Nedlands, WA 6009, Australia

[9] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia

[10] Sir Charles Gairdner Hosp, Dept Pulm Physiol, W Australian Sleep Disorders Res Inst, Nedlands, WA 6009, Australia

[11] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia

[12] Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol, NL-9700 RB Groningen, Netherlands

[13] Univ Freiburg, Ctr Pediat & Adolescent Med, D-79085 Freiburg, Germany

[14] Univ Groningen, Univ Med Ctr, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

[15] Univ Nottingham Hosp, Queens Med Ctr, Div Therapeut, Nottingham NG7 2UH, England

[16] Univ Cologne, Cologne Ctr Genom, D-50923 Cologne, Germany

[17] Sogang Univ, Dept Life Sci, Lab Genom Divers, Seoul 121742, South Korea

[18] SNP Genet Inc, Dept Genet Epidemiol, Seoul 153803, South Korea

[19] Soonchunhyang Univ, Seoul Hosp, Div Allergy & Resp Med, Seoul 140210, South Korea

[20] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland

[21] Soonchunhyang Univ, Div Allergy & Resp Med, Bucheon Hosp, Puchon 420031, South Korea

[22] Copenhagen Univ Hosp, Bispebjerg Hosp, Dept Resp Med, DK-2400 Copenhagen, Denmark

[23] Sct Hans Hosp Boserupve, Res Inst Biol Psychiat, DK-4000 Roskilde, Denmark

[24] Uppsala Univ, Dept Med Sci Inflammat, S-75105 Uppsala, Sweden

[25] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[26] Duke Univ, Sch Med, Durham, NC 27710 USA

[27] Emory Univ, Sch Med, Atlanta, GA 30322 USA

[28] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[29] Univ Otago Sch Med, Vasc Res Grp, Dunedin 9054, New Zealand

[30] Univ Verona, Dept Mother & Child, Sect Biol & Genet, I-37129 Verona, Italy

[31] Univ Verona, Dept Mother & Child, Sect Pediat, I-37129 Verona, Italy

[32] Bolzano Hosp, Dept Pediat, I-39100 Bolzano, Italy

[33] Univ Verona, Sect Internal Med, Dept Clin & Expt Med, I-37129 Verona, Italy

[34] RAM, Lab Mjodd, IS-109 Reykjavik, Iceland

[35] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany

[36] EURAC Res, Inst Med Genet, D-39100 Bozen, Germany

[37] Univ Groningen, Univ Med Ctr, Dept Pulmonol, NL-9700 RB Groningen, Netherlands

来源：

NATURE GENETICS | 2009年 / 41卷 / 03期

关键词：

THYMIC STROMAL LYMPHOPOIETIN; DISEASE; GENE; CYTOKINE; EXPRESSION; RECEPTOR; GENOME; IL-33; MICE; ST2;

D O I：

10.1038/ng.323

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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).

引用

页码：342 / 347

页数：6

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