title: Gene network analysis in a pediatric cohort identifies novel lung function genes.
abstract: Lung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS) of four pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25-75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0 × 10(-3) from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta=1.41 × 10(-7)). The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta=6.29 × 10(-4) - 2.80 × 10(-8) on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations.
authors.affiliation: Division of Pulmonary Medicine and Cystic Fibrosis Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Ong
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McDonough
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.forename: Rosetta
authors.initials: R
authors.lastname: Chiavacci
authors.forename: Frank
authors.initials: F
authors.lastname: Mentch
authors.forename: Jason B
authors.initials: JB
authors.lastname: Caboot
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spergel
authors.forename: Julian L
authors.initials: JL
authors.lastname: Allen
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
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