Preliminary Results from Genome-wide Meta-analysis of Survival Time in Idiopathic Pulmonary Fibrosis

<p><b>Introduction:</b> Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown cause, with few effective treatments available and poor prognosis (median survival time of 3 years). Genome-wide studies have identified variants associated with susceptibility to IPF. Although the effects of those variants on survival time have been investigated, no study has investigated survival time genome-wide for IPF. We set out to identify novel signals of association with IPF survival time and to replicate previous reports that variants in <i>MUC5B</i> that are associated with increased susceptibility to IPF, are paradoxically associated with an increase in survival time.</p><p> </p><p><b>Methods:</b> We performed genome-wide analyses investigating survival time in a UK IPF study and a USA IPF study and meta-analysed the results. Survival analyses were performed on variants with minor allele frequency (MAF)>0.5% in both studies using a Cox Proportional Hazards model. Independent variants meeting meta-analysis <i>P</i><5×10⁻⁶ and <i>P</i><0.05 in each of the separate studies (with consistent direction of effect estimate between studies), are being investigated further in an independent replication dataset.</p><p> </p><p><b>Results:</b> A total of 963 individuals and 7,730,466 variants were included in the final meta-analysis with maximum follow-up of 16.5 years. A total of 79 independent signals (11 with MAF>5%) reached the criteria described above. Consistent with previous reports, the allele in rs35705950 in <i>MUC5B </i>that is associated with increased susceptibility to IPF, shows some association with increased survival time (HR=0.73, 95% CI: [0.61, 0.87], <i>P</i>=5.08×10⁻⁴).</p><p> </p><p><b>Conclusions: </b>This details the first analysis to investigate survival time genome-wide in IPF.</p>