Background: Genome-wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European-ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. Methods: We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype-Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. Results: Variants at the 17q12-21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome-wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood-onset asthma in British white participants in the UK Biobank data. The asthma-associated rs7856856-C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856-CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children. Conclusions: Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12-21 childhood-onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis.
|Journal||Allergy: European Journal of Allergy and Clinical Immunology|
|Publication status||Accepted/In press - 2021|
Bibliographical noteFunding Information:
We acknowledge all participants and thank Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work. This work was supported by the National Research Foundation Grant funded by the Korean Government (NRF‐2019R1F1A1058910, NRF‐2018R1A5A2025079, NRF‐2013R1A1A2062110, and NRF‐2020R1A2B5B02001713), and funded by Research of Korea Centers for Disease Control and Prevention (2017‐NG67003‐00, 2017‐NG67003‐01, 2017‐NG67003‐02). This study was conducted with bioresources from National Biobank of Korea, the Centers for Disease Control and Prevention, Republic of Korea (KBN‐2017‐026). C.O. was supported by NIH grants R01 HL129735 and UG3 OD 023282; N.S. was supported by NIH grant K08 HL153955.
© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy