Shared genetic risk factors and their implications for treatment of IPF and systemic hypertension

Abstract

More than 50% of individuals with idiopathic pulmonary fibrosis (IPF) have co-morbid hypertension. High blood pressure can lead to organ fibrosis or can be a consequence of artery stiffening due to fibrosis. Studies have implicated common processes, such as TGF-{beta} signalling, in both traits regulation. Our goal is to identify shared genetic risk factors for IPF and hypertension. We analysed the genome-wide genetic correlation using LD Score Regression and the largest available genome-wide association studies of clinically defined IPF, and systolic and diastolic blood pressure (SBP and DBP, respectively). We then conducted a genome-wide colocalisation analysis to identify regions with a shared signal at P<10-5 between IPF and either SBP or DBP. There was no genome-wide correlation between IPF and SBP (correlation (95% CI) -0.077(-0.142, -0.011), P=0.022) or DBP (correlation (95% CI) -0.027(-0.093, 0.039), P=0.427). The genome-wide colocalisation identified 8 shared signals, 3 (near MAD1L1, GOLPH3L/HORMAD1, and at 17q21.31) had the same direction of effect on risk of IPF and hypertension and 5 (near TERC, OBFC1, DEPTOR, and at 7q22.1 and 6p21.2) had opposite effects. These findings support that there may be shared fibrotic mechanisms between IPF and hypertension. The opposite effects of variants at specific loci highlight the need for caution when considering therapeutic targeting of these shared pathways for either disease.