Systematic analysis of copy number variation associated with congenital diaphragmatic hernia

Significance This study describes the results of a large-scale case control analysis of copy number variants (CNVs) in a cohort of patients with congenital diaphragmatic hernia (CDH) and a large number of healthy population-matched controls. Using a customized array comparative genomic hybridization system, we have identified six CNVs that are associated with CDH with statistical significance ( P < 0.05). These regions validate several hypothesized CDH candidate genes and identify additional genes and pathways that contribute to the pathogenesis of CDH. The estimated frequency of pathogenic CNVs in this cohort is 13%, which underscores the critical contribution of CNVs in CDH. This study also provides a model approach that is broadly applicable to other structural birth defects and identifies candidates for future functional studies.