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

Klaus Bønnelykke; 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-Møller; Angela Simpson; Beate St Pourcain; Lachlan Coin; Jennie Hui; Eugene H Walters; Carla M T Tiesler; David L Duffy; Graham Jones; Susan M Ring; Wendy L McArdle; Loren Price; Colin F Robertson; Juha Pekkanen; Clara S 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 J 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 S Postma; Adnan Custovic; Craig E Pennell; Marjo-Riitta Jarvelin; Gerard H Koppelman; Nicholas Timpson; Manuel A Ferreira; Hans Bisgaard; A John Henderson; Australian Asthma Genetics Consortium (AAGC)

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, 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-MøllerAngela Simpson, Beate St Pourcain, Lachlan Coin, Jennie Hui, Eugene H Walters, Carla M T Tiesler, David L Duffy, Graham Jones, Susan M Ring, Wendy L McArdle, Loren Price, Colin F Robertson, Juha Pekkanen, Clara S 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 J 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 S Postma, Adnan Custovic, Craig E Pennell, Marjo-Riitta Jarvelin, Gerard H Koppelman, Nicholas Timpson, Manuel A Ferreira, Hans Bisgaard, A John Henderson, Australian Asthma Genetics Consortium (AAGC)

Department of Clinical Medicine

163 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 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
Journal	Nature Genetics
Volume	45
Pages (from-to)	902-906
Number of pages	5
ISSN	1061-4036
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., Strachan, D. P., 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., ... (AAGC), A. A. G. C. (2013). Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nature Genetics, 45, 902-906. https://doi.org/10.1038/ng.2694

Bønnelykke, K, Matheson, MC, Pers, TH, Granell, R, Strachan, DP, 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, Pourcain, BS, Coin, L, Hui, J, Walters, EH, Tiesler, CMT, Duffy, DL, Jones, G, Ring, SM, McArdle, WL, Price, L, Robertson, CF, Pekkanen, J, Tang, CS, 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, DS, Custovic, A, Pennell, CE, Jarvelin, M-R, Koppelman, GH, Timpson, N, Ferreira, MA, Bisgaard, H, Henderson, AJ & (AAGC), AAGC 2013, 'Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization', Nature Genetics, vol. 45, pp. 902-906. https://doi.org/10.1038/ng.2694

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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 Strachan, {David P} and Alves, {Alexessander Couto} 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-M{\o}ller and Angela Simpson and Pourcain, {Beate St} and Lachlan Coin and Jennie Hui and Walters, {Eugene H} and Tiesler, {Carla M T} and Duffy, {David L} and Graham Jones and Ring, {Susan M} and McArdle, {Wendy L} and Loren Price and Robertson, {Colin F} and Juha Pekkanen and Tang, {Clara S} 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 J} 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 Postma, {Dirkje S} and Adnan Custovic and Pennell, {Craig E} and Marjo-Riitta Jarvelin and Koppelman, {Gerard H} and Nicholas Timpson and Ferreira, {Manuel A} and Hans Bisgaard and Henderson, {A John} and (AAGC), {Australian Asthma Genetics Consortium}",

year = "2013",

month = aug,

doi = "10.1038/ng.2694",

language = "English",

volume = "45",

pages = "902--906",

journal = "Nature: New biology",

issn = "1061-4036",

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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 - Strachan, David P

AU - Alves, Alexessander Couto

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-Møller, 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 L

AU - Jones, Graham

AU - Ring, Susan M

AU - McArdle, Wendy L

AU - Price, Loren

AU - Robertson, Colin F

AU - Pekkanen, Juha

AU - Tang, Clara S

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 J

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 S

AU - Custovic, Adnan

AU - Pennell, Craig E

AU - Jarvelin, Marjo-Riitta

AU - Koppelman, Gerard H

AU - Timpson, Nicholas

AU - Ferreira, Manuel A

AU - Bisgaard, Hans

AU - Henderson, A John

AU - (AAGC), Australian Asthma Genetics Consortium

PY - 2013/8

Y1 - 2013/8

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.

U2 - 10.1038/ng.2694

DO - 10.1038/ng.2694

M3 - Journal article

C2 - 23817571

SN - 1061-4036

VL - 45

SP - 902

EP - 906

JO - Nature: New biology

JF - Nature: New biology

ER -

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

Abstract

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