. Author manuscript; available in PMC: 2014 Nov 19.

Published in final edited form as: Nature. 2014 Jan 22;506(7487):179–184. doi: 10.1038/nature12929

Table 1. Summary results for primary hypotheses.

Hypotheses are grouped into four broad categories (a-d). Each is comprised of sub-tests from which we derive global evidence for the broad category (see Supplementary Text). For category a) the broad p-value was generated using Fisher’s exact method on the missense, silent, and loss-of-function (LoF) mutation counts. P-values for category b) were generated using Fisher’s combined probability test to combine the sub-tests. For c) and d) we combined all genes from each sub-test into a single geneset and evaluated enrichment using dnenrich (see main and Supplementary Text). For categories b - d, we separately evaluated two classes of mutation, nonsynonymous (NS) and LoF, making 7 tests in total. Corrected p-values for the broad categories are adjusted by Bonferroni correction for 7 tests. P-values <0.05 (corrected for broad category tests, uncorrected for sub-tests) in bold.

	Hypothesis category	P-value (corrected)		Sub-tests of primary hypotheses	Subtest details	P-value (uncorrected)
(a)	Increased rates of de novo mutations	1.00		NS:S ratio compared to controls^7-10,13-14	Table 2	0.43
(a)	Increased rates of de novo mutations	1.00		LoF:missense ratio compared to controls^7-10,13-14	Table 2	0.37

		NS	LoF			NS	LoF

				Genic recurrence of de novo mutations (current study)	ED Table 2	0.03	0.20
				Enrichment in SZ (literature^12-14) NS de novo genes	Table 4, ED Table 5	0.59	0.21
(b)	Genic recurrence in SCZ	0.0007	0.25	Increased case/control¹⁵ ratio of rare (MAF < 0.1%) LoF variants in de novo genes	Purcell, et al.¹⁵	0.0003	0.0075
				Excess transmission of NS singletons (current study) in de novo genes	-	0.01	0.29
				Enrichment in SZ CNV (literature^1,20) genes	-	0.29	0.66

				Enrichment in ARC/NMDAR genes²⁰	Table 3, ED Figure 4	0.0008	0.006
(c)	Enrichment in candidate genes	0.0098	1.00	Enrichment in PSD genes, excluding ARC/NMDAR genes²⁰	-	0.24	0.53
				Enrichment in FMRP target genes⁹	ED Table 3	0.009	0.37

(d)	Enrichment in autism/ID de novo genes	0.17	0.0055	Enrichment in autism LoF de novo genes^6-9	Table 4, ED Table 5	0.02	0.0007
(d)	Enrichment in autism/ID de novo genes	0.17	0.0055	Enrichment in ID LoF de novo genes^10,11	Table 4, ED Table 5	0.27	0.02