Gene Network Analysis in a Pediatric Cohort Identifies Novel Lung Function Genes

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, FEV(1), FEV(1)/FVC and FEF(25–75%) 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 (p(meta) = 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 p(meta) = 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.