Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

被引：212

作者：

Bonnelykke, Klaus ^{[1
,2
]}

Matheson, Melanie C. ^{[3
]}

Pers, Tune H. ^{[4
,5
,6
,7
]}

Granell, Raquel ^{[8
]}

Strachan, David P. ^{[9
]}

Alves, Alexessander Couto ^{[10
]}

Linneberg, Allan ^{[11
]}

Curtin, John A. ^{[12
]}

Warrington, Nicole M. ^{[13
]}

Standl, Marie ^{[14
]}

Kerkhof, Marjan ^{[15
]}

Jonsdottir, Ingileif ^{[16
,17
]}

Bukvic, Blazenka K. ^{[18
]}

Kaakinen, Marika ^{[19
,20
]}

Sleimann, Patrick ^{[21
,22
]}

Thorleifsson, Gudmar ^{[16
]}

Thorsteinsdottir, Unnur ^{[16
,17
]}

Schramm, Katharina ^{[23
]}

Baltic, Svetlana ^{[24
,25
]}

Kreiner-Moller, Eskil ^{[1
,2
]}

Simpson, Angela ^{[12
]}

St Pourcain, Beate ^{[8
]}

Coin, Lachlan ^{[10
]}

Hui, Jennie ^{[26
,27
,28
,29
]}

Walters, Eugene H. ^{[30
]}

Tiesler, Carla M. T. ^{[14
]}

Duffy, David L. ^{[31
]}

Jones, Graham ^{[32
]}

Ring, Susan M. ^{[8
]}

McArdle, Wendy L. ^{[8
,9
]}

Price, Loren ^{[24
,25
]}

Robertson, Colin F. ^{[33
]}

Pekkanen, Juha ^{[34
,35
]}

Tang, Clara S. ^{[31
]}

Thiering, Elisabeth ^{[14
]}

Montgomery, Grant W. ^{[31
]}

Hartikainen, Anna-Liisa ^{[36
]}

Dharmage, Shyamali C. ^{[3
]}

Husemoen, Lise L. ^{[11
]}

Herder, Christian ^{[37
]}

Kemp, John P. ^{[8
]}

Elliot, Paul ^{[10
]}

James, Alan ^{[29
,38
,39
]}

Waldenberger, Melanie ^{[40
]}

Abramson, Michael J. ^{[41
]}

Fairfax, Benjamin P. ^{[42
]}

Knight, Julian C. ^{[42
]}

Gupta, Ramneek ^{[4
]}

Thompson, Philip J. ^{[24
,25
]}

Holt, Patrick ^{[43
,44
]}

机构：

[1] Univ Copenhagen, COPSAC Copenhagen Prospect Studies Asthma Childho, Gentofte, Denmark

[2] Copenhagen Univ Hosp, Gentofte, Denmark

[3] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[4] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark

[5] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[6] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA

[7] Broad Inst, Cambridge, MA USA

[8] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[9] Univ London, Div Populat Hlth Sci & Educ, London, England

[10] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[11] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[12] Univ Manchester, Univ Hosp South Manchester Natl Hlth Serv NHS Fdn, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[13] Univ Western Australia, Sch Womens & Infants Hlth, Crawley, WA, Australia

[14] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany

[15] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD GRIAC, Dept Epidemiol, Groningen, Netherlands

[16] deCODE Genet, Reykjavik, Iceland

[17] Univ Iceland, Reykjavik, Iceland

[18] Univ Osijek, Gen Hosp Dr Josip Bencev Slavonski Brod, Dept Pediat, Osijek, Croatia

[19] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[20] Univ Oulu, Bioctr Oulu, Oulu, Finland

[21] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Appl Genom, Philadelphia, PA 19104 USA

[22] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Human Genet, Philadelphia, PA 19104 USA

[23] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[24] Univ Western Australia, Lung Inst Western Australia, Perth, WA 6009, Australia

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

[26] PathWest Lab Med Western Australia, Nedlands, WA, Australia

[27] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia

[28] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia

[29] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn, Perth, WA, Australia

[30] Univ Tasmania, Sch Med, Hobart, Tas, Australia

[31] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[32] Univ Western Sydney, Sch Sci & Hlth, Penrith, NSW 1797, Australia

[33] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[34] Natl Inst Hlth & Welf THL, Dept Environm Hlth, Kuopio, Finland

[35] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland

[36] Univ Oulu, Inst Clin Med, Dept Clin Sci Obstet & Gynecol, Oulu, Finland

[37] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany

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

[39] West Australian Sleep Disorders Res Inst, Dept Pulm Physiol, Nedlands, WA, Australia

[40] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany

[41] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia

[42] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[43] Univ Western Australia, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia

[44] Univ Western Australia, Ctr Child Hlth Res, Perth, WA 6009, Australia

[45] Univ Queensland, Queensland Childrens Med Res Inst, WHO Collaborating Ctr Res Childrens Environm Hlth, Brisbane, Qld, Australia

[46] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[47] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[48] Univ Hosp Schleswig Holstein, Dept Dermatol Allergol & Venerol, Kiel, Germany

[49] Univ Groningen, Univ Med Ctr Groningen, GRIAC, Dept Pulmonol, Groningen, Netherlands

[50] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

SUSCEPTIBILITY LOCI; GENE-EXPRESSION; CROHNS-DISEASE; RISK LOCI; ASTHMA; VARIANTS; ATOPY; MECHANISMS; MICRORNAS; NUMBER;

D O I：

10.1038/ng.2694

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

引用

页码：902 / U290

页数：7

共 43 条

[1]

Transcriptional regulation and transformation by MYC proteins [J].

Adhikary, S ;

Eilers, M .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (08) :635-645

[2]

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 [J].

Anderson, Carl A. ;

Boucher, Gabrielle ;

Lees, Charlie W. ;

Franke, Andre ;

D'Amato, Mauro ;

Taylor, Kent D. ;

Lee, James C. ;

Goyette, Philippe ;

Imielinski, Marcin ;

Latiano, Anna ;

Lagace, Caroline ;

Scott, Regan ;

Amininejad, Leila ;

Bumpstead, Suzannah ;

Baidoo, Leonard ;

Baldassano, Robert N. ;

Barclay, Murray ;

Bayless, Theodore M. ;

Brand, Stephan ;

Buening, Carsten ;

Colombel, Jean-Frederic ;

Denson, Lee A. ;

De Vos, Martine ;

Dubinsky, Marla ;

Edwards, Cathryn ;

Ellinghaus, David ;

Fehrmann, Rudolf S. N. ;

Floyd, James A. B. ;

Florin, Timothy ;

Franchimont, Denis ;

Franke, Lude ;

Georges, Michel ;

Glas, Juergen ;

Glazer, Nicole L. ;

Guthery, Stephen L. ;

Haritunians, Talin ;

Hayward, Nicholas K. ;

Hugot, Jean-Pierre ;

Jobin, Gilles ;

Laukens, Debby ;

Lawrance, Ian ;

Lemann, Marc ;

Levine, Arie ;

Libioulle, Cecile ;

Louis, Edouard ;

McGovern, Dermot P. ;

Milla, Monica ;

Montgomery, Grant W. ;

Morley, Katherine I. ;

Mowat, Craig .

NATURE GENETICS, 2011, 43 (03) :246-U94

[3]

Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease [J].

Anderson, Gary P. .

LANCET, 2008, 372 (9643) :1107-1119

[4]

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[5]

Pvt1-encoded microRNAs in oncogenesis [J].

Beck-Engeser, Gabriele B. ;

Lum, Amy M. ;

Huppi, Konrad ;

Caplen, Natasha J. ;

Wang, Bruce B. ;

Wabl, Matthias .

RETROVIROLOGY, 2008, 5 (1)

[6]

Family based association analysis of the IL2 and IL15 genes in allergic disorders [J].

Christensen, U ;

Haagerup, A ;

Binderup, HG ;

Vestbo, J ;

Kruse, TA ;

Borglum, AD .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2006, 14 (02) :227-235

[7]

lumi:: a pipeline for processing Illumina microarray [J].

Du, Pan ;

Kibbe, Warren A. ;

Lin, Simon M. .

BIOINFORMATICS, 2008, 24 (13) :1547-1548

[8]

Genetics of gene expression and its effect on disease [J].

Emilsson, Valur ;

Thorleifsson, Gudmar ;

Zhang, Bin ;

Leonardson, Amy S. ;

Zink, Florian ;

Zhu, Jun ;

Carlson, Sonia ;

Helgason, Agnar ;

Walters, G. Bragi ;

Gunnarsdottir, Steinunn ;

Mouy, Magali ;

Steinthorsdottir, Valgerdur ;

Eiriksdottir, Gudrun H. ;

Bjornsdottir, Gyda ;

Reynisdottir, Inga ;

Gudbjartsson, Daniel ;

Helgadottir, Anna ;

Jonasdottir, Aslaug ;

Jonasdottir, Adalbjorg ;

Styrkarsdottir, Unnur ;

Gretarsdottir, Solveig ;

Magnusson, Kristinn P. ;

Stefansson, Hreinn ;

Fossdal, Ragnheidur ;

Kristjansson, Kristleifur ;

Gislason, Hjortur G. ;

Stefansson, Tryggvi ;

Leifsson, Bjorn G. ;

Thorsteinsdottir, Unnur ;

Lamb, John R. ;

Gulcher, Jeffrey R. ;

Reitman, Marc L. ;

Kong, Augustine ;

Schadt, Eric E. ;

Stefansson, Kari .

NATURE, 2008, 452 (7186) :423-U2

[9]

A common variant on chromosome 11q13 is associated with atopic dermatitis [J].

Esparza-Gordillo, Jorge ;

Weidinger, Stephan ;

Foelster-Holst, Regina ;

Bauerfeind, Anja ;

Ruschendorf, Franz ;

Patone, Giannino ;

Rohde, Klaus ;

Marenholz, Ingo ;

Schulz, Florian ;

Kerscher, Tamara ;

Hubner, Norbert ;

Wahn, Ulrich ;

Schreiber, Stefan ;

Franke, Andre ;

Vogler, Rainer ;

Heath, Simon ;

Baurecht, Hansjoerg ;

Novak, Natalija ;

Rodriguez, Elke ;

Illig, Thomas ;

Lee-Kirsch, Min-Ae ;

Ciechanowicz, Andrzej ;

Kurek, Michael ;

Piskackova, Tereza ;

Macek, Milan ;

Lee, Young-Ae ;

Ruether, Andreas .

NATURE GENETICS, 2009, 41 (05) :596-601

[10]

Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles [J].

Fairfax, Benjamin P. ;

Makino, Seiko ;

Radhakrishnan, Jayachandran ;

Plant, Katharine ;

Leslie, Stephen ;

Dilthey, Alexander ;

Ellis, Peter ;

Langford, Cordelia ;

Vannberg, Fredrik O. ;

Knight, Julian C. .

NATURE GENETICS, 2012, 44 (05) :502-+

← 1 2 3 4 5 →