To interpret CNV findings in a clinically meaningful way is challenging. Essentially it is difficult to prove causal pathogenic effects. Moreover, most child psychiatric disorders, including those that have been found to be associated with CNVs, are multifactorial in origin and not caused by a single risk factor. In many cases, the presence of a specific CNV will not necessarily imply that it played a role in causing disorder, and, for some CNVs, carriers can be unaffected. Inferring causality is further complicated by the high levels of comorbidity between different child psychiatric and developmental disorders. Furthermore, incomplete penetrance, pleiotropic risk effects, and de novo mutations make estimating the risk of disorder recurrence particularly complex. The etiological role of environmental factors and gene–environment interplay in complex disorders should also not be overlooked—nor should the contribution of other classes of genetic variant.
