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Genome-wide association study identifies TNFSF15 associated with childhood asthma

 Kyung Won Kim  ;  Dong Yun Kim  ;  Dankyu Yoon  ;  Ka-Kyung Kim  ;  Haerin Jang  ;  Nathan Schoettler  ;  Eun Gyul Kim  ;  Mi Na Kim  ;  Jung Yeon Hong  ;  Jeom-Kyu Lee  ;  Sangwoo Kim  ;  Carole Ober  ;  Heon Yung Gee  ;  Myung Hyun Sohn 
 ALLERGY, Vol.77(1) : 218-229, 2022-01 
Journal Title
Issue Date
TNFSF15 ; allergic sensitization ; asthma ; children ; genome-wide association study
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.
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Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Dong Yun(김동윤)
Kim, Mina(김미나) ORCID logo https://orcid.org/0000-0002-1675-0688
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
Hong, Jung Yeon(홍정연) ORCID logo https://orcid.org/0000-0003-0406-9956
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