Pulmonary arterial hypertension (PAH) is a rare disease characterised by remodelling of the pulmonary arteries and increased vascular resistance. A genome wide association study (GWAS) of idiopathic/heritable PAH established novel genetic associations. This GWAS identified a novel genomic locus upstream of the SOX17 gene promoter containing two independent signals inside a putative enhancer region. Sox17 is an important transcription factor in human pulmonary artery endothelial cells (hPAECs) and rare pathogenic mutations in SOX17 have previously been linked to PAH. There is allele-specific transcription factor (TF) binding at the enhancer region upstream of SOX17 and PAH-associated variation in this region affects SOX17 expression, hPAEC function and PAH development. This thesis aims to define the TFs binding at the SOX17 locus and downstream pathways and functional changes regulated by Sox17. Also, to explore how SOX17 expression and function can be rescued by novel compounds. Electromobility shift assay (EMSA) have been used to identify TFs which differentially bind to the enhancer locus present upstream of SOX17. These assays have demonstrated differential binding of hPAECs nuclear proteins to the risk and non-risk alleles from a SOX17 GWAS signal. ROR-alpha, has been identified through in silico analysis and antibody supershift assays to be potentially responsible for this binding. siRNA and CRISPR-Inhibition have been used to manipulate SOX17 and the PAH associated loci to determine downstream genes and pathways affected by SOX17 manipulation. Inhibition of a GWAS signal upstream of SOX17 decreases SOX17 expression. Manipulation of SOX17 expression affects PAH-relevant pathways and functions in hPAECs. In-silico analysis has been used to predict compounds which rescue SOX17 dysfunction. Multiple candidate compounds have been tested and show a reversal of gene changes induced by SOX17 in hPAECs. The PAH GWAS signal is now confirmed as an active enhancer site that regulates SOX17, a TF that regulates PAH-relevant pathways and functions in hPAECs. Novel compounds may be able to rescue these functions through restoration of downstream SOX17 targets, and thus be candidates for the treatment of PAH