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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.
J. Allergy Clin. Immunol. 134, 46-55 (2014)
Verlagsversion Volltext
DOI
PMC
BACKGROUND: The fraction of exhaled nitric oxide (Feno) value is a biomarker of eosinophilic airway inflammation and is associated with childhood asthma. Identification of common genetic variants associated with childhood Feno values might help to define biological mechanisms related to specific asthma phenotypes. OBJECTIVE: We sought to identify the genetic variants associated with childhood Feno values and their relation with asthma. METHODS: Feno values were measured in children age 5 to 15 years. In 14 genome-wide association studies (N = 8,858), we examined the associations of approximately 2.5 million single nucleotide polymorphisms (SNPs) with Feno values. Subsequently, we assessed whether significant SNPs were expression quantitative trait loci in genome-wide expression data sets of lymphoblastoid cell lines (n = 1,830) and were related to asthma in a previously published genome-wide association data set (cases, n = 10,365; control subjects: n = 16,110). RESULTS: We identified 3 SNPs associated with Feno values: rs3751972 in LYR motif containing 9 (LYRM9; P = 1.97 × 10-10) and rs944722 in inducible nitric oxide synthase 2 (NOS2; P = 1.28 × 10-9), both of which are located at 17q11.2-q12, and rs8069176 near gasdermin B (GSDMB; P = 1.88 × 10-8) at 17q12-q21. We found a cis expression quantitative trait locus for the transcript soluble galactoside-binding lectin 9 (LGALS9) that is in linkage disequilibrium with rs944722. rs8069176 was associated with GSDMB and ORM1-like 3 (ORMDL3) expression. rs8069176 at 17q12-q21, but not rs3751972 and rs944722 at 17q11.2-q12, were associated with physician-diagnosed asthma. CONCLUSION: This study identified 3 variants associated with Feno values, explaining 0.95% of the variance. Identification of functional SNPs and haplotypes in these regions might provide novel insight into the regulation of Feno values. This study highlights that both shared and distinct genetic factors affect Feno values and childhood asthma.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
12.047
3.035
27
31
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Airway Inflammation ; Asthma Phenotypes ; Biomarker ; Genetics ; Genome-wide Association Study; Genome-wide Association; Complex Traits; Asthma; Children; Galectin-9; Genes; Heritability; Inflammation; Population; Phenotypes
Sprache
englisch
Veröffentlichungsjahr
2014
Prepublished im Jahr
2013
HGF-Berichtsjahr
2013
ISSN (print) / ISBN
0091-6749
e-ISSN
1097-6825
Zeitschrift
The journal of allergy and clinical immunology
Quellenangaben
Band: 134,
Heft: 1,
Seiten: 46-55
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-503900-001
G-503900-003
G-503900-003
PubMed ID
24315451
WOS ID
WOS:000338930300007
Scopus ID
84903700139
Erfassungsdatum
2013-12-11