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@article{Kim:2023:10.1002/clt2.12282,
author = {Kim, H-K and Kang, J-O and Lim, JE and Ha, T-W and Jung, HU and Lee, WJ and Kim, DJ and Baek, EJ and Adcock, IM and Chung, KF and Kim, T-B and Oh, B},
doi = {10.1002/clt2.12282},
journal = {Clinical and Translational Allergy},
pages = {1--14},
title = {Genetic differences according to onset age and lung function in asthma: a cluster analysis},
url = {http://dx.doi.org/10.1002/clt2.12282},
volume = {13},
year = {2023}
}

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TY  - JOUR
AB  - BACKGROUND: The extent of differences between genetic risks associated with various asthma subtypes is still unknown. To better understand the heterogeneity of asthma, we employed an unsupervised method to identify genetic variants specifically associated with asthma subtypes. Our goal was to gain insight into the genetic basis of asthma. METHODS: In this study, we utilized the UK Biobank dataset to select asthma patients (All asthma, n = 50,517) and controls (n = 283,410). We excluded 14,431 individuals who had no information on predicted values of forced expiratory volume in one second percent (FEV1%) and onset age, resulting in a final total of 36,086 asthma cases. We conducted k-means clustering based on asthma onset age and predicted FEV1% using these samples (n = 36,086). Cluster-specific genome-wide association studies were then performed, and heritability was estimated via linkage disequilibrium score regression. To further investigate the pathophysiology, we conducted eQTL analysis with GTEx and gene-set enrichment analysis with FUMA. RESULTS: Clustering resulted in four distinct clusters: early onset asthmanormalLF (early onset with normal lung function, n = 8172), early onset asthmareducedLF (early onset with reduced lung function, n = 8925), late-onset asthmanormalLF (late-onset with normal lung function, n = 12,481), and late-onset asthmareducedLF (late-onset with reduced lung function, n = 6508). Our GWASs in four clusters and in All asthma sample identified 5 novel loci, 14 novel signals, and 51 cluster-specific signals. Among clusters, early onset asthmanormalLF and late-onset asthmareducedLF were the least correlated (rg  = 0.37). Early onset asthmareducedLF showed the highest heritability explained by common variants (h2  = 0.212) and was associated with the largest number of variants (71 single nucleotide polymorphisms). Further, the pathway analysis conducte
AU  - Kim,H-K
AU  - Kang,J-O
AU  - Lim,JE
AU  - Ha,T-W
AU  - Jung,HU
AU  - Lee,WJ
AU  - Kim,DJ
AU  - Baek,EJ
AU  - Adcock,IM
AU  - Chung,KF
AU  - Kim,T-B
AU  - Oh,B
DO  - 10.1002/clt2.12282
EP  - 14
PY  - 2023///
SN  - 2045-7022
SP  - 1
TI  - Genetic differences according to onset age and lung function in asthma: a cluster analysis
T2  - Clinical and Translational Allergy
UR  - http://dx.doi.org/10.1002/clt2.12282
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37488738
UR  - https://onlinelibrary.wiley.com/doi/10.1002/clt2.12282
UR  - http://hdl.handle.net/10044/1/105608
VL  - 13
ER  -

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