Leveraging global multi-ancestry meta-analysis in the study of Idiopathic Pulmonary Fibrosis genetics

Abstract

The research of rare and devastating orphan diseases such as Idiopathic Pulmonary Fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor - the prevalence of IPF is only [~]4-times the incidence of the condition, limiting the recruitment of patients to trials and studies of the underlying biology of the disease. However, global biobanking efforts can dramatically alter the future of IPF research. Here we describe the largest meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine the meta-analysis with the largest available meta-analysis of IPF so far, reaching 11,160 patients and 1,364,410 population controls in analysis. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection, beyond what is known to date. We also note a significant unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.