Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition with poor survival times. We previously published a genome-wide meta-analysis of IPF risk across three studies with independent replication of associated variants in two additional studies. To maximise power and to generate more accurate effect size estimates, we performed a genome-wide meta-analysis across all five studies included in the previous IPF risk genome-wide association studies. We used the distribution of effect sizes across the five studies to assess the replicability of the results and identified five robust novel genetic association signals implicating mTOR (mammalian target of rapamycin) signalling, telomere maintenance and spindle assembly genes in IPF risk.

Trial registration: ClinicalTrials.gov NCT01134822 NCT01110694 NCT00957242 NCT00650091 NCT04016181 NCT01071707 NCT02988388 NCT00075998 NCT01872689 NCT00287729 NCT00287716 NCT01366209.

Keywords: Idiopathic pulmonary fibrosis.

Figure 1

Study design and sample sizes.

Figure 2

Manhattan plot. Each point shows a genetic variant with chromosomal position on the x axis and the −log(p value) on the y axis. The grey dashed line shows the genome-wide significance level (p=5×10⁻⁸). Each signal is labelled with the gene implicated by that signal. Genes in grey are the novel loci that do show evidence of replicability. The plot has been truncated at p=10⁻³⁰