Although multigenerational family studies of ASD are precluded by the low reproductive rate in people with ASD, studies of baby siblings of youth with ASD have been inconsistent in the extent to which the data support the expectations of sex differences in the multifactorial polygenic threshold models. Whereas Ritvo and colleagues 79 and Sumi and colleagues 80 showed increased risk of ASD in younger siblings of female probands with ASD, Ozonoff and colleagues 81 found equal rates of ASD in siblings by sex of the proband. The higher threshold for females than males in the multifactorial threshold model of ASD has been attributed to the higher tolerance for mutational burden in females that has a protective influence on the development of ASD. 82 , 83 Evidence for this female‐protective effect in ASD has been showed in population‐based, 84 family‐based, 85 , 86 , 87 and cohort studies. 88 The female‐protective effect has also been shown in ADHD, 89 and may also apply to schizophrenia. 90 , 91 Genetic factors may also underlie sex differences in ADHD as showed by several
