We have recently proposed that investigation of genomic structural variants (GSVs) in patients with “extreme” obese phenotypes provides an effective route for the identification of novel obesity-associated loci [9]. Initial reports indicate that subjects with unexplained extreme obesity phenotypes may have a higher aggregate frequency of large GSVs (e.g. >0.5 Mb) compared to the general population [10], [11], strongly suggesting that some of the GSVs carried by these unusual patients are responsible for a pronounced, readily-identifiable phenotype with high penetrance. Genes within the regions delineated by such GSVs may also be of direct relevance to obesity in the general population.
