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RISS 인기검색어
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- 저자 : Ersoy Civelek (검색결과 1 건)
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Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function
Mehmet Karaca,Nazente Atceken,Şefayet Karaca,Ersoy Civelek,Bülent E. Şekerel,Renato Polimanti 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.5
Purpose: Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). Methods: Sixteen variants were selected from previous GWAS of childhood/adult asthma and pulmonary function tests. We conducted a phenome-wide association study of these loci in 4,083 traits assessed in the UK Biobank (n = 361,194 participants). Data from the Genotype-Tissue Expression (GTEx) project were used to conduct a transcriptomic analysis with respect to tissues relevant for asthma pathogenesis. A pediatric cohort assessed with the International Study of Asthma and Allergies in Children (ISAAC) Phase II tools was used to further explore the association of these variants with 116 traits related to asthma comorbidities. Results: Our phenome-wide association studies (PheWAS) identified 206 phenotypic associations with respect to the 16 variants identified. In addition to the replication of the phenotypes tested in the discovery GWAS, we observed novel associations related to blood levels of immune cells (eosinophils, neutrophils, monocytes, and lymphocytes) for the asthma-related variants. Conversely, the lung-function variants were associated with phenotypes related to body fat mass. In the ISAAC-assessed cohort, we observed that risk alleles associated with increased fat mass can exacerbate allergic reactions in individuals affected by allergic respiratory diseases. The GTEx-based analysis showed that the variants tested affect the transcriptomic regulation of multiple surrounding genes across several tissues. Conclusions: This study generated novel data regarding the genetics of respiratory diseases and their comorbidities, providing a deep characterization of loci associated with asthma and lung function.
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