jpm-11-00733.pdf (1.4 MB)
Identification of ROBO2 as a potential locus associated with inhaled corticosteroid response in childhood asthma
journal contribution
posted on 2023-06-10, 00:28 authored by Natalia Hernandez-Pacheco, Mario Gorenjak, Jiang Li, Katja Repnik, Susanne J Vijverberg, Vojko Berce, Andrea Jorgensen, Leila Karimi, Maximilian Schieck, Lesly-Anne Samedy-Bates, Roger Tavendale, Jesús Villar, Somnath MukhopadhyaySomnath Mukhopadhyay, Munir Pirmohamed, Katia M C Verhamme, othersInhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A ge-nome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was performed in 166 asthma patients from the SLOVENIA study. Patients with an improvement in lung function =8% were considered as ICS responders. Suggestively associated variants (p-value=5x10-6) were evaluated in an independent study (n=175). Validation of the association with asthma exacerbations despite ICS use was attempted in European (n=2,681) and admixed (n=1,347) populations. Variants previously associated with ICS response were also assessed for replication. As a result, the SNP rs1166980 from the ROBO2 gene was suggestively associated with the change in lung function (OR for G allele: 7.01, 95% CI: 3.29 – 14.93, p=4.61x10-7), although this was not validated in CAMP. ROBO2 showed gene-level evidence of replication with asthma exacerbations despite ICS use in Europeans (minimum p-value=1.44x10-5), but not in admixed individuals. The association of PDE10A-T with ICS response de-scribed by a previous study was validated. This study suggests that ROBO2 could be a potential novel locus for ICS response in Europeans.
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Publication status
- Published
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- Published version
Journal
Journal of personalised medicineISSN
2075-4426Publisher
MDPIExternal DOI
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8Volume
11Page range
1-17Article number
a733Department affiliated with
- Clinical and Experimental Medicine Publications
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- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-07-27First Open Access (FOA) Date
2021-08-03First Compliant Deposit (FCD) Date
2021-08-03Usage metrics
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