In addition, although we propose that the differences in polygenic risk prediction between TS and OCD and between OCD with and without tics are due to divergent genetic architectures, alternative explanations should be considered, such as diagnostic misclassification or differences in case ascertainment between study sites or over time. It is also important to note that we focused on common variation, and that rare inherited variation, unique mutations within individual families, de novo mutations, structural variation and/or epigenetic and non-genetic factors are all likely contributors to the overall etiology of these related disorders. While our initial studies suggested that common variants account for most of the heritability of TS and OCD (10), it is still extremely important to explore all of these potential contributors to disease in order to acquire a full understanding of their relative contributions to TS and OCD.
