Ankylosing spondylitis (AS) is a chronic inflammatory arthritis characterized by inflammation and osteoproliferation in the lower spine and sacroiliac joints. This dysregulated bone growth leads to the fusion of affected joints, resulting in chronic pain and disability. It is considered a complex genetic disorder, with a heritability of around 90%, and has over 100 genetic loci associated through genome-wide association studies (GWAS). An inherent challenge with GWAS is that many of the associated genetic variants lie within the non-coding genome and exhibit linkage disequilibrium (LD). Therefore determining their function, and the genes and pathways they modulate, and thus identify the disease causal variant and its mechanism of action is a major roadblock to progress in this field. Functional genomic approaches are emerging to interpret the non-coding genome and its relationship with disease. This thesis aimed to utilize functional genomic approaches to advance the understanding of the genetic aetiology of AS. CRISPR/Cas9 modulated genome editing was utilized for the functional characterization of two putative enhancers within the ASGWAS associated locus, TNFRSF1A. The generation of large deletions using CRISPR/Cas9 presented unanticipated challenges, including the issue of mosaic cellular clones post CRISPR/Cas9 editing. The methodological issues and how these can be addressed for generating homozygous CRISPR/Cas9 edited cells, harbouring deletions of interest, are discussed. Despite unforeseen complications with CRISPR/Cas9 editing, the two putative enhancers were deleted in induced pluripotent stem cells (iPSCs), which were then differentiated in macrophages. The edited cells then underwent assays to map regions of open chromatin, histone modifications, physical chromatin interactions, and gene expression changes in edited and unedited cells. One of the predicted regulatory regions was found to be an enhancer for TNFRSF1A, and the other was discovered not to be enhancer, but a potential repressor for NCAPD2, located approximately 150kb away. In addition to functional experiments in a model system, this thesis also examined the genome-wide epigenetic differences between AS patients and healthy controls in primary human immune cells. Assay for Transposase Accessible Chromatin Sequencing (ATAC-seq) was used to define regions of chromatin that were differentially open in AS patients. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) was performed to identify differential regions of H3K27ac, denoting active enhancers, and H3K4me3, denoting active promoters. This data was combined with gene expression data to define putative regulatory regions associated with AS and annotate GWAS variants for future functional studies.