Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Johannes Waage; Marie Standl; John A Curtin; Leon E Jessen; Jonathan Thorsen; Chao Tian; Nathan Schoettler; 23andMe Research Team; AAGC collaborators; Carlos Flores; Abdel Abdellaoui; Tarunveer S Ahluwalia; Alexessander C Alves; Andre F S Amaral; Josep M Antó; Andreas Arnold; Amalia Barreto-Luis; Hansjörg Baurecht; Catharina E M van Beijsterveldt; Eugene R Bleecker; Sílvia Bonàs-Guarch; Dorret I Boomsma; Susanne Brix; Supinda Bunyavanich; Esteban G Burchard; Zhanghua Chen; Ivan Curjuric; Adnan Custovic; Herman T den Dekker; Shyamali C Dharmage; Julia Dmitrieva; Liesbeth Duijts; Markus J Ege; W James Gauderman; Michel Georges; Christian Gieger; Frank Gilliland; Raquel Granell; Hongsheng Gui; Torben Hansen; Joachim Heinrich; John Henderson; Natalia Hernandez-Pacheco; Patrick Holt; Medea Imboden; Vincent W V Jaddoe; Marjo-Riitta Jarvelin; Deborah L Jarvis; Kamilla K Jensen; Ellen A Nohr; Hans Bisgaard; David P Strachan; Klaus Bønnelykke

doi:10.1038/s41588-018-0157-1

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Johannes Waage, Marie Standl, John A Curtin, Leon E Jessen, Jonathan Thorsen, Chao Tian, Nathan Schoettler, 23andMe Research Team, AAGC collaborators, Carlos Flores, Abdel Abdellaoui, Tarunveer S Ahluwalia, Alexessander C Alves, Andre F S Amaral, Josep M Antó, Andreas Arnold, Amalia Barreto-Luis, Hansjörg Baurecht, Catharina E M van Beijsterveldt, Eugene R BleeckerSílvia Bonàs-Guarch, Dorret I Boomsma, Susanne Brix, Supinda Bunyavanich, Esteban G Burchard, Zhanghua Chen, Ivan Curjuric, Adnan Custovic, Herman T den Dekker, Shyamali C Dharmage, Julia Dmitrieva, Liesbeth Duijts, Markus J Ege, W James Gauderman, Michel Georges, Christian Gieger, Frank Gilliland, Raquel Granell, Hongsheng Gui, Torben Hansen, Joachim Heinrich, John Henderson, Natalia Hernandez-Pacheco, Patrick Holt, Medea Imboden, Vincent W V Jaddoe, Marjo-Riitta Jarvelin, Deborah L Jarvis, Kamilla K Jensen, Ellen A Nohr, Hans Bisgaard, David P Strachan, Klaus Bønnelykke

Department of Clinical Medicine

35 Citations (Scopus)

Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

Original language	English
Journal	Nature Genetics
Volume	50
Issue number	8
Pages (from-to)	1072-1080
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0157-1
Publication status	Published - 1 Aug 2018

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Waage, J., Standl, M., Curtin, J. A., Jessen, L. E., Thorsen, J., Tian, C., Schoettler, N., 23andMe Research Team, AAGC collaborators, Flores, C., Abdellaoui, A., Ahluwalia, T. S., Alves, A. C., Amaral, A. F. S., Antó, J. M., Arnold, A., Barreto-Luis, A., Baurecht, H., van Beijsterveldt, C. E. M., ... Bønnelykke, K. (2018). Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nature Genetics, 50(8), 1072-1080. https://doi.org/10.1038/s41588-018-0157-1

Waage, J, Standl, M, Curtin, JA, Jessen, LE, Thorsen, J, Tian, C, Schoettler, N, 23andMe Research Team, AAGC collaborators, Flores, C, Abdellaoui, A, Ahluwalia, TS, Alves, AC, Amaral, AFS, Antó, JM, Arnold, A, Barreto-Luis, A, Baurecht, H, van Beijsterveldt, CEM, Bleecker, ER, Bonàs-Guarch, S, Boomsma, DI, Brix, S, Bunyavanich, S, Burchard, EG, Chen, Z, Curjuric, I, Custovic, A, den Dekker, HT, Dharmage, SC, Dmitrieva, J, Duijts, L, Ege, MJ, Gauderman, WJ, Georges, M, Gieger, C, Gilliland, F, Granell, R, Gui, H, Hansen, T, Heinrich, J, Henderson, J, Hernandez-Pacheco, N, Holt, P, Imboden, M, Jaddoe, VWV, Jarvelin, M-R, Jarvis, DL, Jensen, KK, Nohr, EA, Bisgaard, H, Strachan, DP & Bønnelykke, K 2018, 'Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis', Nature Genetics, vol. 50, no. 8, pp. 1072-1080. https://doi.org/10.1038/s41588-018-0157-1

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title = "Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis",

abstract = "Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.",

author = "Johannes Waage and Marie Standl and Curtin, {John A} and Jessen, {Leon E} and Jonathan Thorsen and Chao Tian and Nathan Schoettler and {23andMe Research Team} and {AAGC collaborators} and Carlos Flores and Abdel Abdellaoui and Ahluwalia, {Tarunveer S} and Alves, {Alexessander C} and Amaral, {Andre F S} and Ant{\'o}, {Josep M} and Andreas Arnold and Amalia Barreto-Luis and Hansj{\"o}rg Baurecht and {van Beijsterveldt}, {Catharina E M} and Bleecker, {Eugene R} and S{\'i}lvia Bon{\`a}s-Guarch and Boomsma, {Dorret I} and Susanne Brix and Supinda Bunyavanich and Burchard, {Esteban G} and Zhanghua Chen and Ivan Curjuric and Adnan Custovic and {den Dekker}, {Herman T} and Dharmage, {Shyamali C} and Julia Dmitrieva and Liesbeth Duijts and Ege, {Markus J} and Gauderman, {W James} and Michel Georges and Christian Gieger and Frank Gilliland and Raquel Granell and Hongsheng Gui and Torben Hansen and Joachim Heinrich and John Henderson and Natalia Hernandez-Pacheco and Patrick Holt and Medea Imboden and Jaddoe, {Vincent W V} and Marjo-Riitta Jarvelin and Jarvis, {Deborah L} and Jensen, {Kamilla K} and Nohr, {Ellen A} and Hans Bisgaard and Strachan, {David P} and Klaus B{\o}nnelykke",

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doi = "10.1038/s41588-018-0157-1",

language = "English",

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T1 - Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

AU - Waage, Johannes

AU - Standl, Marie

AU - Curtin, John A

AU - Jessen, Leon E

AU - Thorsen, Jonathan

AU - Tian, Chao

AU - Schoettler, Nathan

AU - 23andMe Research Team

AU - AAGC collaborators

AU - Flores, Carlos

AU - Abdellaoui, Abdel

AU - Ahluwalia, Tarunveer S

AU - Alves, Alexessander C

AU - Amaral, Andre F S

AU - Antó, Josep M

AU - Arnold, Andreas

AU - Barreto-Luis, Amalia

AU - Baurecht, Hansjörg

AU - van Beijsterveldt, Catharina E M

AU - Bleecker, Eugene R

AU - Bonàs-Guarch, Sílvia

AU - Boomsma, Dorret I

AU - Brix, Susanne

AU - Bunyavanich, Supinda

AU - Burchard, Esteban G

AU - Chen, Zhanghua

AU - Curjuric, Ivan

AU - Custovic, Adnan

AU - den Dekker, Herman T

AU - Dharmage, Shyamali C

AU - Dmitrieva, Julia

AU - Duijts, Liesbeth

AU - Ege, Markus J

AU - Gauderman, W James

AU - Georges, Michel

AU - Gieger, Christian

AU - Gilliland, Frank

AU - Granell, Raquel

AU - Gui, Hongsheng

AU - Hansen, Torben

AU - Heinrich, Joachim

AU - Henderson, John

AU - Hernandez-Pacheco, Natalia

AU - Holt, Patrick

AU - Imboden, Medea

AU - Jaddoe, Vincent W V

AU - Jarvelin, Marjo-Riitta

AU - Jarvis, Deborah L

AU - Jensen, Kamilla K

AU - Nohr, Ellen A

AU - Bisgaard, Hans

AU - Strachan, David P

AU - Bønnelykke, Klaus

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

AB - Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

U2 - 10.1038/s41588-018-0157-1

DO - 10.1038/s41588-018-0157-1

M3 - Letter

C2 - 30013184

SN - 1061-4036

VL - 50

SP - 1072

EP - 1080

JO - Nature: New biology

JF - Nature: New biology

IS - 8

ER -

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

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