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

Klaus Bonnelykke; Melanie C Matheson; Tune H Pers; Raquel Granell; David P Strachan; Alexessander Couto Alves; Allan Linneberg; John A Curtin; Nicole M Warrington; Marie Standl; Marjan Kerkhof; Ingileif Jonsdottir; Blazenka K Bukvic; Marika Kaakinen; Patrick Sleimann; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Katharina Schramm; Svetlana Baltic; Eskil Kreiner-Moller; Angela Simpson; Beate St Pourcain; Lachlan Coin; Jennie Hui; Eugene H Walters; Carla M T Tiesler; David Duffy; Graham Jones; Guy B Marks; Patrick Danoy; Desiree Meszaros; Catherine Hayden; Anjali K Henders; Brett Chapman; Andrew J Kemp; Faang Cheah; Melissa C Southey; Mary Roberts; Euan R Tovey; Graham G Giles; Li P Chung; Paul S Thomas; Ian Feather; Suzanna Temple; John Beilby; Stephen Morrison; David P Johns; Chalermchai Mitrpant; Brad Shelton; Mark Jenkins; Warwick J Britton; Andrew S Kemp; Peter Le Souef; John L Hopper; Stephen R Leeder; Bill Musk; Nicholas G Martin; Matthew A Brown; Susan M Ring; Wendy L McArdle; Loren Price; Colin F Robertson; Juha Pekkanen; Clara Tang; Elisabeth Thiering; Grant W Montgomery; Anna-Liisa Hartikainen; Shyamali C Dharmage; Lise L Husemoen; Christian Herder; John P Kemp; Paul Elliot; Alan James; Melanie Waldenberger; Michael John Abramson; Benjamin P Fairfax; Julian C Knight; Ramneek Gupta; Philip J Thompson; Patrick Holt; Peter Sly; Joel N Hirschhorn; Mario Blekic; Stephan Weidinger; Hakon Hakonarsson; Kari Stefansson; Joachim Heinrich; Dirkje Postma; Adnan Custovic; Craig Pennell; Marjo-Riitta Jarvelin; Gerard H Koppelman; Nicholas Timpson; Manuel Ferreira; Hans Bisgaard; A John Henderson

doi:10.1038/ng.2694

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

Klaus Bonnelykke, Melanie C Matheson, Tune H Pers, Raquel Granell, David P Strachan, Alexessander Couto Alves, Allan Linneberg, John A Curtin, Nicole M Warrington, Marie Standl, Marjan Kerkhof, Ingileif Jonsdottir, Blazenka K Bukvic, Marika Kaakinen, Patrick Sleimann, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Katharina Schramm, Svetlana Baltic, Eskil Kreiner-MollerAngela Simpson, Beate St Pourcain, Lachlan Coin, Jennie Hui, Eugene H Walters, Carla M T Tiesler, David Duffy, Graham Jones, Guy B Marks, Patrick Danoy, Desiree Meszaros, Catherine Hayden, Anjali K Henders, Brett Chapman, Andrew J Kemp, Faang Cheah, Melissa C Southey, Mary Roberts, Euan R Tovey, Graham G Giles, Li P Chung, Paul S Thomas, Ian Feather, Suzanna Temple, John Beilby, Stephen Morrison, David P Johns, Chalermchai Mitrpant, Brad Shelton, Mark Jenkins, Warwick J Britton, Andrew S Kemp, Peter Le Souef, John L Hopper, Stephen R Leeder, Bill Musk, Nicholas G Martin, Matthew A Brown, Susan M Ring, Wendy L McArdle, Loren Price, Colin F Robertson, Juha Pekkanen, Clara Tang, Elisabeth Thiering, Grant W Montgomery, Anna-Liisa Hartikainen, Shyamali C Dharmage, Lise L Husemoen, Christian Herder, John P Kemp, Paul Elliot, Alan James, Melanie Waldenberger, Michael John Abramson, Benjamin P Fairfax, Julian C Knight, Ramneek Gupta, Philip J Thompson, Patrick Holt, Peter Sly, Joel N Hirschhorn, Mario Blekic, Stephan Weidinger, Hakon Hakonarsson, Kari Stefansson, Joachim Heinrich, Dirkje Postma, Adnan Custovic, Craig Pennell, Marjo-Riitta Jarvelin, Gerard H Koppelman, Nicholas Timpson, Manuel Ferreira, Hans Bisgaard, A John Henderson

Epidemiology and Preventive Medicine Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

190 Citations (Scopus)

Abstract

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 1 10,056 controls and followed up the top SNP at each of 26 loci in 6,11114 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.

Original language	English
Pages (from-to)	902 - 906
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	8
DOIs	https://doi.org/10.1038/ng.2694
Publication status	Published - 2013

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Bonnelykke, K., Matheson, M. C., Pers, T. H., Granell, R., Strachan, D. P., Couto Alves, A., Linneberg, A., Curtin, J. A., Warrington, N. M., Standl, M., Kerkhof, M., Jonsdottir, I., Bukvic, B. K., Kaakinen, M., Sleimann, P., Thorleifsson, G., Thorsteinsdottir, U., Schramm, K., Baltic, S., ... Henderson, A. J. (2013). Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nature Genetics, 45(8), 902 - 906. https://doi.org/10.1038/ng.2694

@article{a101018cd2b348dca723815e0807e7d4,

title = "Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization",

abstract = "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 1 10,056 controls and followed up the top SNP at each of 26 loci in 6,11114 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.",

author = "Klaus Bonnelykke and Matheson, {Melanie C} and Pers, {Tune H} and Raquel Granell and Strachan, {David P} and {Couto Alves}, Alexessander and Allan Linneberg and Curtin, {John A} and Warrington, {Nicole M} and Marie Standl and Marjan Kerkhof and Ingileif Jonsdottir and Bukvic, {Blazenka K} and Marika Kaakinen and Patrick Sleimann and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Katharina Schramm and Svetlana Baltic and Eskil Kreiner-Moller and Angela Simpson and Pourcain, {Beate St} and Lachlan Coin and Jennie Hui and Walters, {Eugene H} and Tiesler, {Carla M T} and David Duffy and Graham Jones and Marks, {Guy B} and Patrick Danoy and Desiree Meszaros and Catherine Hayden and Henders, {Anjali K} and Brett Chapman and Kemp, {Andrew J} and Faang Cheah and Southey, {Melissa C} and Mary Roberts and Tovey, {Euan R} and Giles, {Graham G} and Chung, {Li P} and Thomas, {Paul S} and Ian Feather and Suzanna Temple and John Beilby and Stephen Morrison and Johns, {David P} and Chalermchai Mitrpant and Brad Shelton and Mark Jenkins and Britton, {Warwick J} and Kemp, {Andrew S} and {Le Souef}, Peter and Hopper, {John L} and Leeder, {Stephen R} and Bill Musk and Martin, {Nicholas G} and Brown, {Matthew A} and Ring, {Susan M} and McArdle, {Wendy L} and Loren Price and Robertson, {Colin F} and Juha Pekkanen and Clara Tang and Elisabeth Thiering and Montgomery, {Grant W} and Anna-Liisa Hartikainen and Dharmage, {Shyamali C} and Husemoen, {Lise L} and Christian Herder and Kemp, {John P} and Paul Elliot and Alan James and Melanie Waldenberger and Abramson, {Michael John} and Fairfax, {Benjamin P} and Knight, {Julian C} and Ramneek Gupta and Thompson, {Philip J} and Patrick Holt and Peter Sly and Hirschhorn, {Joel N} and Mario Blekic and Stephan Weidinger and Hakon Hakonarsson and Kari Stefansson and Joachim Heinrich and Dirkje Postma and Adnan Custovic and Craig Pennell and Marjo-Riitta Jarvelin and Koppelman, {Gerard H} and Nicholas Timpson and Manuel Ferreira and Hans Bisgaard and Henderson, {A John}",

year = "2013",

doi = "10.1038/ng.2694",

language = "English",

volume = "45",

pages = "902 -- 906",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "8",

}

Bonnelykke, K, Matheson, MC, Pers, TH, Granell, R, Strachan, DP, Couto Alves, A, Linneberg, A, Curtin, JA, Warrington, NM, Standl, M, Kerkhof, M, Jonsdottir, I, Bukvic, BK, Kaakinen, M, Sleimann, P, Thorleifsson, G, Thorsteinsdottir, U, Schramm, K, Baltic, S, Kreiner-Moller, E, Simpson, A, Pourcain, BS, Coin, L, Hui, J, Walters, EH, Tiesler, CMT, Duffy, D, Jones, G, Marks, GB, Danoy, P, Meszaros, D, Hayden, C, Henders, AK, Chapman, B, Kemp, AJ, Cheah, F, Southey, MC, Roberts, M, Tovey, ER, Giles, GG, Chung, LP, Thomas, PS, Feather, I, Temple, S, Beilby, J, Morrison, S, Johns, DP, Mitrpant, C, Shelton, B, Jenkins, M, Britton, WJ, Kemp, AS, Le Souef, P, Hopper, JL, Leeder, SR, Musk, B, Martin, NG, Brown, MA, Ring, SM, McArdle, WL, Price, L, Robertson, CF, Pekkanen, J, Tang, C, Thiering, E, Montgomery, GW, Hartikainen, A-L, Dharmage, SC, Husemoen, LL, Herder, C, Kemp, JP, Elliot, P, James, A, Waldenberger, M, Abramson, MJ, Fairfax, BP, Knight, JC, Gupta, R, Thompson, PJ, Holt, P, Sly, P, Hirschhorn, JN, Blekic, M, Weidinger, S, Hakonarsson, H, Stefansson, K, Heinrich, J, Postma, D, Custovic, A, Pennell, C, Jarvelin, M-R, Koppelman, GH, Timpson, N, Ferreira, M, Bisgaard, H & Henderson, AJ 2013, 'Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization', Nature Genetics, vol. 45, no. 8, pp. 902 - 906. https://doi.org/10.1038/ng.2694

TY - JOUR

T1 - Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

AU - Bonnelykke, Klaus

AU - Matheson, Melanie C

AU - Pers, Tune H

AU - Granell, Raquel

AU - Strachan, David P

AU - Couto Alves, Alexessander

AU - Linneberg, Allan

AU - Curtin, John A

AU - Warrington, Nicole M

AU - Standl, Marie

AU - Kerkhof, Marjan

AU - Jonsdottir, Ingileif

AU - Bukvic, Blazenka K

AU - Kaakinen, Marika

AU - Sleimann, Patrick

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Schramm, Katharina

AU - Baltic, Svetlana

AU - Kreiner-Moller, Eskil

AU - Simpson, Angela

AU - Pourcain, Beate St

AU - Coin, Lachlan

AU - Hui, Jennie

AU - Walters, Eugene H

AU - Tiesler, Carla M T

AU - Duffy, David

AU - Jones, Graham

AU - Marks, Guy B

AU - Danoy, Patrick

AU - Meszaros, Desiree

AU - Hayden, Catherine

AU - Henders, Anjali K

AU - Chapman, Brett

AU - Kemp, Andrew J

AU - Cheah, Faang

AU - Southey, Melissa C

AU - Roberts, Mary

AU - Tovey, Euan R

AU - Giles, Graham G

AU - Chung, Li P

AU - Thomas, Paul S

AU - Feather, Ian

AU - Temple, Suzanna

AU - Beilby, John

AU - Morrison, Stephen

AU - Johns, David P

AU - Mitrpant, Chalermchai

AU - Shelton, Brad

AU - Jenkins, Mark

AU - Britton, Warwick J

AU - Kemp, Andrew S

AU - Le Souef, Peter

AU - Hopper, John L

AU - Leeder, Stephen R

AU - Musk, Bill

AU - Martin, Nicholas G

AU - Brown, Matthew A

AU - Ring, Susan M

AU - McArdle, Wendy L

AU - Price, Loren

AU - Robertson, Colin F

AU - Pekkanen, Juha

AU - Tang, Clara

AU - Thiering, Elisabeth

AU - Montgomery, Grant W

AU - Hartikainen, Anna-Liisa

AU - Dharmage, Shyamali C

AU - Husemoen, Lise L

AU - Herder, Christian

AU - Kemp, John P

AU - Elliot, Paul

AU - James, Alan

AU - Waldenberger, Melanie

AU - Abramson, Michael John

AU - Fairfax, Benjamin P

AU - Knight, Julian C

AU - Gupta, Ramneek

AU - Thompson, Philip J

AU - Holt, Patrick

AU - Sly, Peter

AU - Hirschhorn, Joel N

AU - Blekic, Mario

AU - Weidinger, Stephan

AU - Hakonarsson, Hakon

AU - Stefansson, Kari

AU - Heinrich, Joachim

AU - Postma, Dirkje

AU - Custovic, Adnan

AU - Pennell, Craig

AU - Jarvelin, Marjo-Riitta

AU - Koppelman, Gerard H

AU - Timpson, Nicholas

AU - Ferreira, Manuel

AU - Bisgaard, Hans

AU - Henderson, A John

PY - 2013

Y1 - 2013

N2 - 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 1 10,056 controls and followed up the top SNP at each of 26 loci in 6,11114 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.

AB - 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 1 10,056 controls and followed up the top SNP at each of 26 loci in 6,11114 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.

UR - http://www.nature.com/ng/journal/v45/n8/pdf/ng.2694.pdf

U2 - 10.1038/ng.2694

DO - 10.1038/ng.2694

M3 - Article

VL - 45

SP - 902

EP - 906

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -

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

Abstract

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