The aim of this D.Phil. thesis was to enrich current knowledge of genetic susceptibility and severity factors in rheumatoid arthritis (RA), a common complex disease with an estimated heritability of approximately 60% in the Northern European population. A DNA resource from 760 clinically well-characterised British Caucasian RA patients was established for use in association studies to investigate candidate genes. The previously reported association of PTPN22 (1858C/T rs2476601) and rheumatoid factor positive disease was observed (p=0.004). Examination of PTPN22 gene for differential allelic expression (DAE) in different peripheral blood mononuclear cell populations from RA patients was undertaken. A DAE of 20% or more in 8 RA patients (p< 10^-5) was observed, indicating possible existence of cis-acting genetic variation. PTPN22 DAE in a number of cell types was demonstrated in 4 RA patients and there were also different allelic ratios between these cell populations (p_c < 0.05). MHC class II expression is controlled at the transcription level by MHC class II transactivator (CIITA) and is mainly dependent on the transcription of its gene MHC2TA. The frequency of MHC2TA (-168A/G, rs3087456) polymorphism in RA cases did not differ from those in controls. Minor allele frequencies were higher in HLA-DRB1 shared epitope negative and DRB1*04 negative patients (p=0.01 and p=0.03 respectively). Further direct sequencing followed by single nucleotide polymorphism genotyping and haplotype analysis did not reveal significant skewing in the haplotype distribution. Polymorphisms in the IL-1A and IL-1B promoter can influence gene expression and these were investigated for association. The IL-1B (-1464 C/G, rs1143623) G allele was found to be less common in the RA group (p=0.01). Meta-analysis revealed statistically significant association between IL-1B (-511 A/G, rs16944) and RA (p=0.02). Although the importance of studied markers in predicting disease susceptibility is modest, together with future findings these results may help to provide better insight concerning the RA disease process.