Fig. 1. Idiopathic pulmonary fibrosis genetic discovery and replication study design.

We combined whole-exome sequence (WES) and whole-genome sequence (WGS) data from a total of 804 cases enroled in either the PROFILE study or the UK Biobank. Controls comprised of 219,627 UK Biobank participants. We harmonised the case-control cohort based on ancestry, relatedness, and gender, resulting in a test cohort total of 752 cases and 119,055 controls screened for non-respiratory disease. We filtered out sites that were differentially covered between cases and controls. We then performed two analyses: an exome-wide variant-level association test (ExWAS) and rare variant collapsing analysis. Variants from the ExWAS with p < 0.01 were then reviewed in the FinnGen cohort. Collapsing analyses were also combined with previously published results from an independent case-control study⁶. MAF = minor allele frequency.