An alternative explanation for the results is that ascertainment and diagnostic biases, where female individuals are more likely to be diagnosed with ADHD if they have a more severe phenotypic presentation, could be involved. Individuals who receive one diagnosis become the focus of clinical attention and are more likely to receive subsequent diagnoses, whereas individuals with less complex phenotypes might not come to clinical attention. If female individuals are routinely underdiagnosed with ADHD or other neurodevelopmental disorders, this issue may disproportionately affect ascertainment of female cases, leading to the observed pattern of results. Other possible sources of bias include typical exclusion criteria for diagnosing ADHD (e.g., ID, ASD) and the possibility of an inflated false positive rate of diagnoses due to diagnostic uncertainty and change over time. We limited the impact of the latter by considering diagnoses only in individuals with at least two reported diagnoses. Although the results are consistent with increased etiological heterogeneity in female individuals with ADHD, studies of rare variation are required to rule out these alternative explanations.
