Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids

Susanne J. H. Vijverberg; Natalia Hernandez-Pacheco; Niloufar Farzan; Ben Francis; Carlos Flores; Maximilian Schieck; Patricia Soares; Leila Karimi; Roger Tavendale; Vojko Berce; Katja Repnik; Katia M. C. Verhamme; Uros Potocnik; Somnath Mukhopadhyay; Munir Pirmohamed; Colin N. Palmer; Steve W. Turner; Daniel B. Hawcutt; Michael Kabesch; Maria Pino-Yanes; Anke-Hilse Maitland-van der Zee

doi:10.1002/pds.4275

Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids

Susanne J. H. Vijverberg, Natalia Hernandez-Pacheco, Niloufar Farzan, Ben Francis, Carlos Flores, Maximilian Schieck, Patricia Soares, Leila Karimi, Roger Tavendale, Vojko Berce, Katja Repnik, Katia M. C. Verhamme, Uros Potocnik, Somnath Mukhopadhyay, Munir Pirmohamed, Colin N. Palmer, Steve W. Turner, Daniel B. Hawcutt, Michael Kabesch, Maria Pino-YanesAnke-Hilse Maitland-van der Zee

Population Health and Genomics

Research output: Contribution to journal › Meeting abstract › peer-review

Abstract

Background:Inhaled corticosteroids (ICS) are themost common asthma controller medication. How-ever, a high proportion of patients does not respondto this medication and suffer exacerbations.

Objectives:To identify genes associated with asthma exacerbations in European children with a reported use of ICS.

Methods:We performed a genome-wide association study (GWAS) meta-analysis across three European asthma cohorts (PACMAN, PASS and follow MAGICS)that participated in the Pharmacogenomics in Childhood Asthma consortium. We studied 1,204 asthmatic children treated with ICS. The primary outcome measure was asthma exacerbations, defined as the use of oral corticosteroids, asthma-related hospitalizations or asthma-related emergency room visits. Imputation of genetic variants was performed using the Haplotype Reference Consortium as reference panel by means of the Michigan Imputation Server. Association testing of 7.5 million genetic variants with minor allele frequency≥1% was per-formed using logistic regression models and results were meta-analyzed.

Results:A total of 74 genetic variants were suggestively associated with asthma exacerbations despite the use of ICS (p≤5×106). The most significant variants were located in 9 different loci (minimum p-value = 2.3 × 107), including one gene previously identified as associated with ICS response in Asian populations (ALLC). Additionally, novel associations were revealed in biologically plausible genes with drug metabolism functions and in genes belonging to the Wnt/β-catenin signaling pathway.

Conclusions: We identified several novel genes suggestively associated with asthma exacerbations despite the use of ICS. Validation will be performed in further independent studies.

Original language	English
Pages (from-to)	25-26
Journal	Pharmacoepidemiology and Drug Safety
Volume	26
DOIs	https://doi.org/10.1002/pds.4275
Publication status	Published - 22 Aug 2017

Access to Document

10.1002/pds.4275

Cite this

Vijverberg, S. J. H., Hernandez-Pacheco, N., Farzan, N., Francis, B., Flores, C., Schieck, M., Soares, P., Karimi, L., Tavendale, R., Berce, V., Repnik, K., Verhamme, K. M. C., Potocnik, U., Mukhopadhyay, S., Pirmohamed, M., Palmer, C. N., Turner, S. W., Hawcutt, D. B., Kabesch, M., ... Maitland-van der Zee, A.-H. (2017). Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids. Pharmacoepidemiology and Drug Safety, 26, 25-26. https://doi.org/10.1002/pds.4275

@article{02c21a0c38b14030b5e891c660a411b8,

title = "Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids",

abstract = "Background:Inhaled corticosteroids (ICS) are themost common asthma controller medication. How-ever, a high proportion of patients does not respondto this medication and suffer exacerbations.Objectives:To identify genes associated with asthma exacerbations in European children with a reported use of ICS.Methods:We performed a genome-wide association study (GWAS) meta-analysis across three European asthma cohorts (PACMAN, PASS and follow MAGICS)that participated in the Pharmacogenomics in Childhood Asthma consortium. We studied 1,204 asthmatic children treated with ICS. The primary outcome measure was asthma exacerbations, defined as the use of oral corticosteroids, asthma-related hospitalizations or asthma-related emergency room visits. Imputation of genetic variants was performed using the Haplotype Reference Consortium as reference panel by means of the Michigan Imputation Server. Association testing of 7.5 million genetic variants with minor allele frequency≥1% was per-formed using logistic regression models and results were meta-analyzed.Results:A total of 74 genetic variants were suggestively associated with asthma exacerbations despite the use of ICS (p≤5×106). The most significant variants were located in 9 different loci (minimum p-value = 2.3 × 107), including one gene previously identified as associated with ICS response in Asian populations (ALLC). Additionally, novel associations were revealed in biologically plausible genes with drug metabolism functions and in genes belonging to the Wnt/β-catenin signaling pathway.Conclusions: We identified several novel genes suggestively associated with asthma exacerbations despite the use of ICS. Validation will be performed in further independent studies.",

author = "Vijverberg, {Susanne J. H.} and Natalia Hernandez-Pacheco and Niloufar Farzan and Ben Francis and Carlos Flores and Maximilian Schieck and Patricia Soares and Leila Karimi and Roger Tavendale and Vojko Berce and Katja Repnik and Verhamme, {Katia M. C.} and Uros Potocnik and Somnath Mukhopadhyay and Munir Pirmohamed and Palmer, {Colin N.} and Turner, {Steve W.} and Hawcutt, {Daniel B.} and Michael Kabesch and Maria Pino-Yanes and {Maitland-van der Zee}, Anke-Hilse",

year = "2017",

month = aug,

day = "22",

doi = "10.1002/pds.4275",

language = "English",

volume = "26",

pages = "25--26",

journal = "Pharmacoepidemiology and Drug Safety",

issn = "1053-8569",

publisher = "Wiley",

}

Vijverberg, SJH, Hernandez-Pacheco, N, Farzan, N, Francis, B, Flores, C, Schieck, M, Soares, P, Karimi, L, Tavendale, R, Berce, V, Repnik, K, Verhamme, KMC, Potocnik, U, Mukhopadhyay, S, Pirmohamed, M, Palmer, CN, Turner, SW, Hawcutt, DB, Kabesch, M, Pino-Yanes, M & Maitland-van der Zee, A-H 2017, 'Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids', Pharmacoepidemiology and Drug Safety, vol. 26, pp. 25-26. https://doi.org/10.1002/pds.4275

TY - JOUR

T1 - Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids

AU - Vijverberg, Susanne J. H.

AU - Hernandez-Pacheco, Natalia

AU - Farzan, Niloufar

AU - Francis, Ben

AU - Flores, Carlos

AU - Schieck, Maximilian

AU - Soares, Patricia

AU - Karimi, Leila

AU - Tavendale, Roger

AU - Berce, Vojko

AU - Repnik, Katja

AU - Verhamme, Katia M. C.

AU - Potocnik, Uros

AU - Mukhopadhyay, Somnath

AU - Pirmohamed, Munir

AU - Palmer, Colin N.

AU - Turner, Steve W.

AU - Hawcutt, Daniel B.

AU - Kabesch, Michael

AU - Pino-Yanes, Maria

AU - Maitland-van der Zee, Anke-Hilse

PY - 2017/8/22

Y1 - 2017/8/22

N2 - Background:Inhaled corticosteroids (ICS) are themost common asthma controller medication. How-ever, a high proportion of patients does not respondto this medication and suffer exacerbations.Objectives:To identify genes associated with asthma exacerbations in European children with a reported use of ICS.Methods:We performed a genome-wide association study (GWAS) meta-analysis across three European asthma cohorts (PACMAN, PASS and follow MAGICS)that participated in the Pharmacogenomics in Childhood Asthma consortium. We studied 1,204 asthmatic children treated with ICS. The primary outcome measure was asthma exacerbations, defined as the use of oral corticosteroids, asthma-related hospitalizations or asthma-related emergency room visits. Imputation of genetic variants was performed using the Haplotype Reference Consortium as reference panel by means of the Michigan Imputation Server. Association testing of 7.5 million genetic variants with minor allele frequency≥1% was per-formed using logistic regression models and results were meta-analyzed.Results:A total of 74 genetic variants were suggestively associated with asthma exacerbations despite the use of ICS (p≤5×106). The most significant variants were located in 9 different loci (minimum p-value = 2.3 × 107), including one gene previously identified as associated with ICS response in Asian populations (ALLC). Additionally, novel associations were revealed in biologically plausible genes with drug metabolism functions and in genes belonging to the Wnt/β-catenin signaling pathway.Conclusions: We identified several novel genes suggestively associated with asthma exacerbations despite the use of ICS. Validation will be performed in further independent studies.

AB - Background:Inhaled corticosteroids (ICS) are themost common asthma controller medication. How-ever, a high proportion of patients does not respondto this medication and suffer exacerbations.Objectives:To identify genes associated with asthma exacerbations in European children with a reported use of ICS.Methods:We performed a genome-wide association study (GWAS) meta-analysis across three European asthma cohorts (PACMAN, PASS and follow MAGICS)that participated in the Pharmacogenomics in Childhood Asthma consortium. We studied 1,204 asthmatic children treated with ICS. The primary outcome measure was asthma exacerbations, defined as the use of oral corticosteroids, asthma-related hospitalizations or asthma-related emergency room visits. Imputation of genetic variants was performed using the Haplotype Reference Consortium as reference panel by means of the Michigan Imputation Server. Association testing of 7.5 million genetic variants with minor allele frequency≥1% was per-formed using logistic regression models and results were meta-analyzed.Results:A total of 74 genetic variants were suggestively associated with asthma exacerbations despite the use of ICS (p≤5×106). The most significant variants were located in 9 different loci (minimum p-value = 2.3 × 107), including one gene previously identified as associated with ICS response in Asian populations (ALLC). Additionally, novel associations were revealed in biologically plausible genes with drug metabolism functions and in genes belonging to the Wnt/β-catenin signaling pathway.Conclusions: We identified several novel genes suggestively associated with asthma exacerbations despite the use of ICS. Validation will be performed in further independent studies.

U2 - 10.1002/pds.4275

DO - 10.1002/pds.4275

M3 - Meeting abstract

SN - 1053-8569

VL - 26

SP - 25

EP - 26

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

ER -

Genome-Wide Association Study of Asthma Exacerbations in European Children Treated with Inhaled Corticosteroids

Abstract

Access to Document

Fingerprint

Cite this