Genotype-phenotype relationships in patients with idiopathic pulmonary arterial hypertension / investigating variants in other rare forms of pulmonary hypertension

Study code

Lead researcher
Dr Allan Lawrie

Study type
Data only

Institution or company
University of Sheffield (Department of Infection, Immunity & Cardiovascular Disease)

Researcher type

Speciality area
Cardiovascular Disease, Genomics and Rare Diseases


We have identified a cohort of patients with very severe pulmonary arterial hypertension associated with lung disease. We have performed whole exome sequencing, transcriptomics, miRNA arrays and proteomics and identified a number of high-impact variants of interest and wish to explore these within the cohort of pulmonary arterial hypertension patients within the NIHR Rare Diseases BioResource.


Harbaum, L., Rhodes, C., Wharton, J., Lawrie, A., Karnes, J., Desai, A., et al. (2022). 'Mining the plasma proteome for insights into the molecular pathology of pulmonary arterial hypertension.' Am J Respir Crit Care Med 205(12):1449-1460 (link)


We present the largest analysis of circulating proteins in PAH to date and identified new pQTL revealed by the analyses in disease samples. MR analysis of protein targets advocated strongly by our observational associations suggests that therapeutic interventions that inhibit NET4 activity and augment TSP2 activity may be beneficial in this rare condition. This is supported by serial measurements in relatives at risk for heritable PAH, where changes in NET4 and TSP2 levels reported the onset of the disease.