Extended Data Table 1a. Stratification of de novo mutations based on polygenic burden, presence of a ‘pathogenic’ CNV, or poor scholastic achievement.

Ratios of nonsynonymous to synonymous (NS:S) and loss-of-function to missense (LoF:missense) de novo mutations were compared (Fisher’s exact test) between those found in individuals with a high polygenic score (top 50%) and those in the individuals in the bottom 50% of the polygenic score distribution (scores previously generated for this sample⁴⁴). Individuals were additionally split based on the presence of a ‘pathogenic’ CNV. A ‘pathogenic’ CNV was defined as either a de novo CNV identified for these samples in Kirov, et al.²⁰, or a CNV associated with psychiatric disease¹. P-values were computed using Fisher’s exact test as in Table 2.

	Probands with top 50% of polygenic scores		Probands with bottom 50% of polygenic scores	Probands with top 50% of polygenic scores or a ‘pathogenic’ CNV		Probands with bottom 50% of polygenic scores and no ‘pathogenic’ CNV
NS	210		229	228		214
S	71		66	74		63
Ratio	2.96		3.47	3.08		3.4
p	0.43			0.63
LoF	24		29	26		27
missense	182		196	198		183
Ratio	0.13		0.15	0.13		0.15
p	0.77			0.77