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The impact of genomic structural variation on the human phenotype and the degree to which it contributes to the unexplained heritability of complex disease is of considerable interest, particularly as rapidly rising rates of metabolic disorders have placed increased impetus on identification of genetic factors influencing individual susceptibility to obesity. The work presented in this thesis focusses on the role of genomic structural variants (GSVs) in the modulation of adiposity and pathogenesis of obesity. Common CNVs were investigated in two severe obesity case-control study samples. Eight intragenic and five intergenic CNVs were significantly associated with increased susceptibility to obesity (P < 2.0??10-6), eight of which were located within variable number of tandem repeats (VNTRs). Investigation of a complex copy number variable region on 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene revealed the presence of two complex VNTRs flanking a common deletion. We have developed a novel VNTR association algorithm, VNTRtest, which we employed to show significant association of the DOCK5 VNTRs with childhood and adult obesity (P=3.7??10-9 and P=3.1??10-3, respectively), as well as independent association between the 3,975bp deletion and obesity (P=1.6??10-3). We have also shown copy number at the multi-allelic salivary amylase gene (AMY1) to be strongly associated with both adiposity and obesity susceptibility, replicating this finding in six Caucasian study samples. Carriers of low versus high copy numbers at AMY1 showed increased risk of obesity (OR [95%CI]=10.50 [5.19-22.53]; P=2.71??10-10). Copy-numbers at this locus were also correlated with serum amylase levels, which also showed inverse correlation with body mass index. Additionally, rare duplications above 500kb were significantly enriched in child and adult obesity (P=8.89??10-3 and P=9.78??10-3, respectively). Functional annotation analysis also revealed enrichment for genes associated with schizophrenia within GSVs identified in obese subjects (P=2.2??10-5). In summary, this thesis presents multiple novel GSV associations with obesity as well as methodology for GSV genotyping and association testing. It is hoped that the work described in this thesis may contribute towards elucidation of the role of genomic structural variation in complex disease.