Extending our pathway analyses to all 234 genes implicated by gene expression or deleterious variants, we observed enrichment of genes related to “signalling events mediated by the Hedgehog family” pathway. Hedgehog signalling plays a crucial role in early development. Three members of this pathway, PTCH1, TGFB2 and HHIP, have been previously reported as likely causal genes underlying lung function association signals35. In this study, we additionally report PTHLH, encoding a parathyroid hormone-like hormone, and CDON¸ encoding a Hedgehog co-receptor, as likely causal genes (the latter at a novel signal). Of the 73 well-imputed variants available in children, we show correlation (r=0.62) between variant effect size estimates with those in adults. Should this pattern of correlation apply across all 97 lung-function-associated variants, then this would suggest that many of these variants may act, at least in part, via effects on lung development. Elastic fibre pathways were over-represented; products of elastin degradation have been shown to be elevated during acute exacerbations of COPD 36,37. In addition, degradation of elastin by excess neutrophil-released elastase in the lung leads to emphysema in individuals with
