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

Klaus Bønnelykke; Melanie C Matheson; Tune H Pers; Raquel Granell; Strachan David P; Alexessander Couto Alves; Allan Linneberg; John A Curtin; Nicole M Warrington; Marie Standl; Marjan Kerkhof; I Jonsdottir; Blazenka Kljaic Bukvic; Marika Kaakinen; Patrick Sleimann; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Katharina Schramm; Svetlana Baltic; Eskil Kreiner-Møller; Angela Simpson; M U B St. Pourcain; Lachlan J M Coin; Jennie Hui; Haydn Walters; Carla M T Tiesler; David Duffy; Graham Jones; Susan M Ring; Wendy L McArdle; Loren Price; Colin Robertson; Juha Pekkanen; Clara Tang; Elisabeth Thiering; Grant Montgomery; Anna-Liisa Hartikainen; Shyamali Dharmage; Lise L Husemoen; Christian Herder; John P Kemp; Paul Elliot; Alan James; Melanie Waldenberger; Michael Abramson; Ben P Fairfax; Julian Knight; Ramneek Gupta; Phil Thompson; Patrick  Holt; Peter Sly; Joel N Hirschhorn; Mario Blekic; Stephan Weidinger; Hakon Hakonsarson; Kari Stefansson; Joachim Heinrich; Dirkje S Postma; Adnan Custovic; Craig E Pennell; Marjo-Riitta Jarvelin; Gerard H Koppelman; Nicholas J Timpson; Manuel Ferreira; Hans Bisgaard; A J W Henderson

doi:10.1038/ng.2694

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

Klaus Bønnelykke, Melanie C Matheson, Tune H Pers, Raquel Granell, Strachan David P, Alexessander Couto Alves, Allan Linneberg, John A Curtin, Nicole M Warrington, Marie Standl, Marjan Kerkhof, I Jonsdottir, Blazenka Kljaic Bukvic, Marika Kaakinen, Patrick Sleimann, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Katharina Schramm, Svetlana Baltic, Eskil Kreiner-MøllerAngela Simpson, M U B St. Pourcain, Lachlan J M Coin, Jennie Hui, Haydn Walters, Carla M T Tiesler, David Duffy, Graham Jones, Susan M Ring, Wendy L McArdle, Loren Price, Colin Robertson, Juha Pekkanen, Clara Tang, Elisabeth Thiering, Grant Montgomery, Anna-Liisa Hartikainen, Shyamali Dharmage, Lise L Husemoen, Christian Herder, John P Kemp, Paul Elliot, Alan James, Melanie Waldenberger, Michael Abramson, Ben P Fairfax, Julian Knight, Ramneek Gupta, Phil Thompson, Patrick Holt, Peter Sly, Joel N Hirschhorn, Mario Blekic, Stephan Weidinger, Hakon Hakonsarson, Kari Stefansson, Joachim Heinrich, Dirkje S Postma, Adnan Custovic, Craig E Pennell, Marjo-Riitta Jarvelin, Gerard H Koppelman, Nicholas J Timpson, Manuel Ferreira, Hans Bisgaard, A J W Henderson

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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 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.

Original language	English
Pages (from-to)	902-906
Journal	Nature Genetics
Volume	45
Issue number	8
Early online date	30 Jun 2013
DOIs	https://doi.org/10.1038/ng.2694
Publication status	Published - Aug 2013

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Bønnelykke, K., Matheson, M. C., Pers, T. H., Granell, R., David P, S., Alves, A. C., 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. W. (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{7c5a6f74bcf64c2e9d52ac3dda2d8ed4,

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 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.",

author = "Klaus B{\o}nnelykke and Matheson, {Melanie C} and Pers, {Tune H} and Raquel Granell and {David P}, Strachan and Alves, {Alexessander Couto} and Allan Linneberg and Curtin, {John A} and Warrington, {Nicole M} and Marie Standl and Marjan Kerkhof and I Jonsdottir and Bukvic, {Blazenka Kljaic} and Marika Kaakinen and Patrick Sleimann and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Katharina Schramm and Svetlana Baltic and Eskil Kreiner-M{\o}ller and Angela Simpson and {St. Pourcain}, {M U B} and Coin, {Lachlan J M} and Jennie Hui and Haydn Walters and Tiesler, {Carla M T} and David Duffy and Graham Jones and Ring, {Susan M} and McArdle, {Wendy L} and Loren Price and Colin Robertson and Juha Pekkanen and Clara Tang and Elisabeth Thiering and Grant Montgomery and Anna-Liisa Hartikainen and Shyamali Dharmage and Husemoen, {Lise L} and Christian Herder and Kemp, {John P} and Paul Elliot and Alan James and Melanie Waldenberger and Michael Abramson and Fairfax, {Ben P} and Julian Knight and Ramneek Gupta and Phil Thompson and Patrick Holt and Peter Sly and Hirschhorn, {Joel N} and Mario Blekic and Stephan Weidinger and Hakon Hakonsarson and Kari Stefansson and Joachim Heinrich and Postma, {Dirkje S} and Adnan Custovic and Pennell, {Craig E} and Marjo-Riitta Jarvelin and Koppelman, {Gerard H} and Timpson, {Nicholas J} and Manuel Ferreira and Hans Bisgaard and Henderson, {A J W}",

year = "2013",

month = aug,

doi = "10.1038/ng.2694",

language = "English",

volume = "45",

pages = "902--906",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

number = "8",

}

Bønnelykke, K, Matheson, MC, Pers, TH, Granell, R, David P, S, Alves, AC, 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-Møller, E, Simpson, A, St. Pourcain, MUB, Coin, LJM, Hui, J, Walters, H, Tiesler, CMT, Duffy, D, Jones, G, Ring, SM, McArdle, WL, Price, L, Robertson, C, Pekkanen, J, Tang, C, Thiering, E, Montgomery, G, Hartikainen, A-L, Dharmage, S, Husemoen, LL, Herder, C, Kemp, JP, Elliot, P, James, A, Waldenberger, M, Abramson, M, Fairfax, BP, Knight, J, Gupta, R, Thompson, P, Holt, P, Sly, P, Hirschhorn, JN, Blekic, M, Weidinger, S, Hakonsarson, H, Stefansson, K, Heinrich, J, Postma, DS, Custovic, A, Pennell, CE, Jarvelin, M-R, Koppelman, GH, Timpson, NJ, Ferreira, M, Bisgaard, H & Henderson, AJW 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

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

AU - Bønnelykke, Klaus

AU - Matheson, Melanie C

AU - Pers, Tune H

AU - Granell, Raquel

AU - David P, Strachan

AU - Alves, Alexessander Couto

AU - Linneberg, Allan

AU - Curtin, John A

AU - Warrington, Nicole M

AU - Standl, Marie

AU - Kerkhof, Marjan

AU - Jonsdottir, I

AU - Bukvic, Blazenka Kljaic

AU - Kaakinen, Marika

AU - Sleimann, Patrick

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Schramm, Katharina

AU - Baltic, Svetlana

AU - Kreiner-Møller, Eskil

AU - Simpson, Angela

AU - St. Pourcain, M U B

AU - Coin, Lachlan J M

AU - Hui, Jennie

AU - Walters, Haydn

AU - Tiesler, Carla M T

AU - Duffy, David

AU - Jones, Graham

AU - Ring, Susan M

AU - McArdle, Wendy L

AU - Price, Loren

AU - Robertson, Colin

AU - Pekkanen, Juha

AU - Tang, Clara

AU - Thiering, Elisabeth

AU - Montgomery, Grant

AU - Hartikainen, Anna-Liisa

AU - Dharmage, Shyamali

AU - Husemoen, Lise L

AU - Herder, Christian

AU - Kemp, John P

AU - Elliot, Paul

AU - James, Alan

AU - Waldenberger, Melanie

AU - Abramson, Michael

AU - Fairfax, Ben P

AU - Knight, Julian

AU - Gupta, Ramneek

AU - Thompson, Phil

AU - Holt, Patrick

AU - Sly, Peter

AU - Hirschhorn, Joel N

AU - Blekic, Mario

AU - Weidinger, Stephan

AU - Hakonsarson, Hakon

AU - Stefansson, Kari

AU - Heinrich, Joachim

AU - Postma, Dirkje S

AU - Custovic, Adnan

AU - Pennell, Craig E

AU - Jarvelin, Marjo-Riitta

AU - Koppelman, Gerard H

AU - Timpson, Nicholas J

AU - Ferreira, Manuel

AU - Bisgaard, Hans

AU - Henderson, A J W

PY - 2013/8

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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 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.

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 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.

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U2 - 10.1038/ng.2694

DO - 10.1038/ng.2694

M3 - Article (Academic Journal)

C2 - 23817571

SN - 1061-4036

VL - 45

SP - 902

EP - 906

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

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

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