Fig. 2

Sex-differential ASD risk can be represented by a multiple-threshold liability/FPE model. a Under a multiple threshold liability/female-protective effect (FPE) model, risk or liability for ASD is quantitative and distributed in the population, and males and females have different minimum liability thresholds that are sufficient to lead to an ASD diagnosis. The tail of the distribution filled in gray indicates those individuals in the population with diagnosed ASD. b A closer look at the region marked with a green, dotted box in a. A key prediction from the FPE model is that among diagnosed individuals, females will have greater ASD liability than males. A secondary prediction is that non-diagnosed females may carry, or be exposed to, relatively high ASD liability but they do not present symptoms that meet criteria for diagnosis; mothers of autistic children may include such females. c Examples of sex-differential biological factors proposed to contribute to males’ and females’ shifted liability thresholds and differential risk for ASD. Figure adapted from Werling and Geschwind [46]