Citation

BibTex format

@article{Piga:2026:10.1183/23120541.00327-2026,
author = {Piga, NN and Portelli, MA and Shrine, N and Chen, J and Packer, R and Coley, K and Williams, AT and Batini, C and John, C and Lutz, SM and Voorhies, KR and Levin, AM and Zounemat-Kermani, N and Gern, JE and Gold, DR and Hartert, TV and Jackson, DJ and Johnson, CC and Khurana, Hershey GK and Miller, RL and Seroogy, CM and Zoratti, EM and Sin, DD and van, den Berge M and Bossé, Y and Hall, RJ and Shaw, D and Pogson, ZEK and Fogarty, A and Heaney, LG and Mansur, AH and Chaudhuri, R and Thomson, NC and Holloway, JW and Chung, KF and Blakey, JD and Wain, LV and Ober, C and Wu, AC and Adcock, IM and Hall, IP and Brightling, CE and Lassi, G and Sayers, I and Fawcett, KA},
doi = {10.1183/23120541.00327-2026},
journal = {ERJ Open Res},
title = {Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.},
url = {http://dx.doi.org/10.1183/23120541.00327-2026},
volume = {12},
year = {2026}
}
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TY  - JOUR
AB  - BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.
AU  - Piga,NN
AU  - Portelli,MA
AU  - Shrine,N
AU  - Chen,J
AU  - Packer,R
AU  - Coley,K
AU  - Williams,AT
AU  - Batini,C
AU  - John,C
AU  - Lutz,SM
AU  - Voorhies,KR
AU  - Levin,AM
AU  - Zounemat-Kermani,N
AU  - Gern,JE
AU  - Gold,DR
AU  - Hartert,TV
AU  - Jackson,DJ
AU  - Johnson,CC
AU  - Khurana,Hershey GK
AU  - Miller,RL
AU  - Seroogy,CM
AU  - Zoratti,EM
AU  - Sin,DD
AU  - van,den Berge M
AU  - Bossé,Y
AU  - Hall,RJ
AU  - Shaw,D
AU  - Pogson,ZEK
AU  - Fogarty,A
AU  - Heaney,LG
AU  - Mansur,AH
AU  - Chaudhuri,R
AU  - Thomson,NC
AU  - Holloway,JW
AU  - Chung,KF
AU  - Blakey,JD
AU  - Wain,LV
AU  - Ober,C
AU  - Wu,AC
AU  - Adcock,IM
AU  - Hall,IP
AU  - Brightling,CE
AU  - Lassi,G
AU  - Sayers,I
AU  - Fawcett,KA
DO  - 10.1183/23120541.00327-2026
PY  - 2026///
SN  - 2312-0541
TI  - Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.
T2  - ERJ Open Res
UR  - http://dx.doi.org/10.1183/23120541.00327-2026
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42682922
VL  - 12
ER  -
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