Asthma is the most common disease of childhood in the westernised world, affecting one child in seven in the United Kingdom alone. It is a complex disease involving both genetic and environmental factors. The financial burden for sufferers approximates £1 billion per annum in the UK and 80% of the sum is attributable to the patients with the severe, “difficult/therapy-resistant” form of the disease. Previously, a Genome Wide Association Study (GWAS) for childhood asthma identified a number of loci significantly associated to the disease. The top ten SNP hits with the highest association (0.0001>P>0.00001) were chosen for an investigation of their importance in cases of severe asthma, both childhood and adult. The 10 SNPs were genotyped in 397 adults and 94 children using TaqMan® SNP Genotyping Assays. Genotyping data was analysed for genetic associations to the severe asthma phenotype using chi-squared tests. Control data was obtained from data generated in the original GWAS for the British controls. SNP rs6585018 located in the PDCD4 gene predicted promoter was found to be significantly associated to childhood asthma (P=3.4x10-7). Additional markers on the PDCD4 gene area were chosen to be typed in 116 severe asthmatic children and 145 healthy children from the UK. SNPs rs6585018 (P=0.005), rs1322997 (P=0.005) in the predicted promoter area and rs34104444 (P=0.01) in exon 5 were associated to severe asthma. The three SNPs were also correlated with PDCD4 transcript levels. PDCD4 genomic area was analysed in silico and ElectroMobility Shift Assay (EMSA) experiments were designed for the rs6548018 alleles to examine how they alter transcription factor binding sites. SNP rs6585018 was found to alter the binding site of the Myb transcription factor possibly altering the expression of PDCD4 gene. This study has provided insights into the genetic factors that are involved in disease aetiology of severe asthma.