Douard E, Zeribi A, Schramm C, et al. - Up to 20% of individuals with autism are identified to harbor deleterious copy number variants (CNVs). In their recent work, researchers developed statistical models to determine the effect size on IQ of all CNVs, including undocumented ones. They here performed extension of this model to autism susceptibility. Two autism populations (Simons Simplex Collection and MSSNG) and two unselected populations (IMAGEN and Saguenay Youth Study) were assessed for the CNVs. The effect of CNVs on IQ and autism risk was best explained by the “probability of being loss-of-function intolerant” (pLI). IQ decreases by 2.6 points in autism and unselected populations in correlation with deletion of 1 point of pLI. Threefold smaller effect of duplications was observed on IQ. Findings suggest that IQ less influences the autism risk conferred by duplications compared with deletions. The model used in this study, trained on CNVs encompassing > 4,500 genes, indicates highly polygenic properties of gene dosage with respect to autism risk and IQ loss. These models will aid in interpreting CNVs detected in the clinic.