The absence of extensive sequencing data currently precludes analogous analyses of rare genetic variants. Instead, to evaluate whether such variants play differential roles in male and female individuals with ADHD, we used risk for comorbid brain-related developmental disorders (i.e., autism spectrum disorder [ASD], intellectual disability [ID], epilepsy, motor developmental delay) and rare syndromic phenotypes (i.e., congenital malformations, syndromes related to chromosomal abnormalities) as proxies for possible presence of de novo or rare segregating alleles. Rare, highly deleterious (including noninherited) genetic variation has been implicated in such phenotypes 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. Indeed, comorbid ID has been associated with an increased likelihood that an individual with ADHD is a carrier of a large, rare copy number variant (CNV) (26). It has also long been known that rare genetic syndromes (e.g., fragile X syndrome, velocardiofacial syndrome) are associated with ADHD 27, 28. Evidence for an increase in comorbid conditions in female individuals with ADHD, when compared with affected male individuals, would imply a more severe syndromal phenotypic presentation of ADHD in a higher proportion of
