Phenotypic and molecular characterization of risk loci associated with asthma and lung function

Karaca, Mehmet; Atçeken, Nazente; Karaca, Şefayet; Civelek, Ersoy; Şekerel, Bülent Enİs; Polimanti, Renato

Phenotypic and molecular characterization of risk loci associated with asthma and lung function

dc.authorid	0000-0002-7688-4223
dc.authorid	0000-0002-2020-9659
dc.authorid	0000-0002-3645-3875
dc.authorid	0000-0002-1780-4801
dc.authorid	0000-0003-4232-3396
dc.authorid	0000-0003-0745-6046
dc.contributor.author	Karaca, Mehmet
dc.contributor.author	Atçeken, Nazente
dc.contributor.author	Karaca, Şefayet
dc.contributor.author	Civelek, Ersoy
dc.contributor.author	Şekerel, Bülent Enİs
dc.contributor.author	Polimanti, Renato
dc.date.accessioned	2021-02-05T07:51:23Z
dc.date.available	2021-02-05T07:51:23Z
dc.date.issued	2020
dc.department	Sabire Yazıcı Fen Edebiyat Fakültesi
dc.description	Karaca, Mehmet ( Aksaray, Yazar ) Atçeken, Nazente ( Aksaray, Yazar ) *Yücetepe, Aysun ( Aksaray, Yazar )
dc.description.abstract	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.
dc.identifier.doi	10.4168/aair.2020.12.5.806
dc.identifier.endpage	820	en_US
dc.identifier.issn	2092-7355
dc.identifier.issue	5	en_US
dc.identifier.pmid	32638561
dc.identifier.scopusquality	Q2
dc.identifier.startpage	806	en_US
dc.identifier.uri	https:/dx.doi.org/10.4168/aair.2020.12.5.806
dc.identifier.uri	https://hdl.handle.net/20.500.12451/7733
dc.identifier.volume	12	en_US
dc.identifier.wos	WOS:000547386200007
dc.identifier.wosquality	Q2
dc.indekslendigikaynak	Web of Science
dc.indekslendigikaynak	Scopus
dc.indekslendigikaynak	PubMed
dc.language.iso	en
dc.publisher	Korean Academy of Asthma, Allergy and Clinical Immunology
dc.relation.ispartof	Allergy, Asthma and Immunology Research
dc.relation.publicationcategory	Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Allergy
dc.subject	Asthma
dc.subject	Genetics
dc.subject	Loci
dc.subject	Lung Function
dc.subject	Transcriptome
dc.title	Phenotypic and molecular characterization of risk loci associated with asthma and lung function
dc.type	Article