Genome-Wide Analyses of Survival Time in the Rare Disease, Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with poor prognosis (median survival time of 3 years) characterised by scarring of lung tissue. IPF has been linked with a number of environmental and genetic factors; the strongest genetic association being in the MUC5B gene. Despite this the pathogenesis of IPF is still unclear and more needs to be done to understand the genetic basis of IPF.

We are conducting analyses genome-wide to investigate survival time in 565 IPF cases. Previous evidence suggests variants associated with susceptibility to IPF may not be associated with survival time or may even have effects in the opposite direction. A genome-wide association case-control study was also conducted allowing variants associated with susceptibility to IPF and survival time to be directly compared.

This analysis has raised a number of methodological issues such as which survival models to fit, how well survival models fit variants of different allele frequencies, and how these influence power. The statistical power relates not only to the allele frequency but also to the number of events in each genotype group. In this study, we fitted a Cox proportional hazards model, which makes no assumption about the distribution of the underlying baseline hazard function, and compared findings with those from alternative models.