@article{f66badf6fb8a40d18411af1db68127ac,
title = "Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.",
abstract = "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.",
keywords = "Airway inflammation, asthma phenotypes, biomarker, genetics, genome-wide association study",
author = "{van der Valk}, {Ralf J P} and Liesbeth Duijts and Timpson, {Nicolas J} and Salam, {Muhammad T} and Marie Standl and Curtin, {John A} and Jon Genuneit and Marjan Kerhof and Eskil Kreiner-M{\o}ller and Alejandro C{\'a}ceres and Anna Gref and Liang, {Liming L} and Taal, {H Rob} and Emmanuelle Bouzigon and Florence Demenais and Rachel Nadif and Carole Ober and Thompson, {Emma E} and Karol Estrada and Albert Hofman and Uitterlinden, {Andr{\'e} G} and {van Duijn}, Corn{\'e}lia and Fernando Rivadeneira and Xia Li and Eckel, {Sandrah P} and Kiros Berhane and Gauderman, {W James} and Raquel Granell and Evans, {David M} and {St Pourcain}, Beate and Wendy McArdle and Kemp, {John P} and Smith, {George Davey} and Tiesler, {Carla M T} and Claudia Flexeder and Angela Simpson and Murray, {Clare S} and Oliver Fuchs and Postma, {Dirkje S} and Klaus B{\o}nnelykke and Maties Torrent and Martin Andersson and Patrick Sleiman and Hakon Hakonarson and Cookson, {William O} and Moffatt, {Miriam F} and Lavinia Paternoster and Erik Mel{\'e}n and Jordi Sunyer and Hans Bisgaard and Koppelman, {Gerard H} and Markus Ege and Adnan Custovic and Joachim Heinrich and Gilliland, {Frank D} and Henderson, {Alexander J} and Jaddoe, {Vincent W V} and {de Jongste}, {Johan C}",
note = "097117, Wellcome Trust, United KingdomG0600705, Medical Research Council, United KingdomG1000758, Medical Research Council, United KingdomG1000758B, Medical Research Council, United KingdomG9815508, Medical Research Council, United KingdomK22 ES022987, NIEHS NIH HHS, United StatesMC_UU_12013/3, Medical Research Council, United KingdomMC_UU_12013/4, Medical Research Council, United KingdomMR/J012165/1, Medical Research Council, United KingdomP01 ES009581, NIEHS NIH HHS, United StatesP01 ES011627, NIEHS NIH HHS, United StatesP30 ES007048, NIEHS NIH HHS, United StatesR01 HL061768, NHLBI NIH HHS, United StatesR01 HL076647, NHLBI NIH HHS, United StatesR01 HL085197, NHLBI NIH HHS, United StatesR01 HL085197, NHLBI NIH HHS, United StatesWT083431MA, Wellcome Trust, United Kingdom",
year = "2014",
month = jul,
doi = "10.1016/j.jaci.2013.08.053",
language = "English",
volume = "134",
pages = "46--55",
journal = "The Journal of allergy and clinical immunology",
issn = "1097-6825",
publisher = "Mosby, Incorporated",
number = "1",
}