While the replications of previous findings underline the strength of our study, the focus on consistently associated common CNVs for early-onset (extreme) obesity using an agnostic genome-wide approach is also accompanied by weaknesses. First of all, our follow-up/replication step using tagging SNPs has focused on only 2 of all 20 candidate CNVRs-albeit those with the strongest association signals. Thus, it is conceivable that additional regions could be true positive findings. However, given their weaker association signals in both of our deletion samples, larger replication samples than the one used by us will be required to rule out false-negative findings. This is underlined by the results of our array-based replication analyses supporting four additional CNVRs of all 20 candidate CNVRs. Secondly, our study clearly has limited detection power to comprehensively assess CNV at a genome-wide level. None of the tested CNVs achieved a stringent genome-wide significance level and for those that could be replicated only moderate effects (odds ratio of ∼1.2) were observable. Thus, our observation for early-onset (extreme) obesity underlines the recent finding that common CNVs are unlikely candidates to
