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

<div><p>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 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 <i>INTS12</i> locus association with FEV1 (p_meta = 1.41<b>×</b>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<b>.</b></p></div

Study participant characteristics.

<p>Study participant characteristics.</p

Top functional annotation networks associated with lung function variables in Caucasian cohort.

<p>Top functional annotation networks associated with lung function variables in Caucasian cohort.</p

Functional analysis results: Benjamini-Hochberg corrected p-values for glycoprotein term association with lung function variables in pediatric and adult cohorts.

<p>Functional analysis results: Benjamini-Hochberg corrected p-values for glycoprotein term association with lung function variables in pediatric and adult cohorts.</p