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; 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; Ingileif Jónsdóttir; Michael Kabesch; Jaakko Kaprio; The 23andMe Research Team; AAGC collaborators

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
, 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, Ingileif Jónsdóttir, Michael Kabesch, Jaakko Kaprio, The 23andMe Research Team, AAGC collaborators

^*Corresponding author for this work

Department of Biotechnology and Biomedicine

Imperial College London
University of Greifswald
Icahn School of Medicine at Mount Sinai
University of California at San Francisco
University of Southern California
Erasmus University Rotterdam
University of Melbourne
University of Liege
Telethon Kids Institute
University of Oulu
University Children’s Hospital Regensburg (KUNO)
National Institute for Health and Welfare
Ludwig Maximilian University of Munich
University of Copenhagen
Helmholtz Zentrum München - German Research Center for Environmental Health
University of Manchester
23andMe Inc.
The University of Chicago
Hospital Universitario Nuestra Senora de Candelaria
Vrije Universiteit Amsterdam
Barcelona Institute for Global Health
Kiel University
University of Arizona
Polytechnic University of Catalonia
University of Basel
University of Bristol
Henry Ford Health System
deCODE Genetics
University of Helsinki

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Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries^1,2. 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
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0157-1
Publication status	Published - 2018

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Waage, J., Standl, M., Curtin, J. A., Jessen, L. E., Thorsen, J., Tian, C., Schoettler, N., 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., Bleecker, E. R., Bonàs-Guarch, S., ... AAGC collaborators (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

@article{d0c7c2a6449f4014a149ea488d123edd,

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 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 Jarvelin, \{Marjo Riitta\} and Jarvis, \{Deborah L.\} and Jensen, \{Kamilla K.\} and Ingileif J{\'o}nsd{\'o}ttir and Michael Kabesch and Jaakko Kaprio and \{The 23andMe Research Team\} and \{AAGC collaborators\}",

year = "2018",

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

language = "English",

volume = "50",

pages = "1072--1080",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

Waage, J, Standl, M, Curtin, JA, Jessen, LE, Thorsen, J, Tian, C, Schoettler, N, 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, MR, Jarvis, DL, Jensen, KK, Jónsdóttir, I, Kabesch, M, Kaprio, J, The 23andMe Research Team & AAGC collaborators 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

TY - JOUR

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 - 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 - Jónsdóttir, Ingileif

AU - Kabesch, Michael

AU - Kaprio, Jaakko

AU - The 23andMe Research Team

AU - AAGC collaborators

PY - 2018

Y1 - 2018

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 - Journal article

C2 - 30013184

AN - SCOPUS:85049975477

SN - 1061-4036

VL - 50

SP - 1072

EP - 1080

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

Abstract

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