Table 2. Geneset analysis of secondary autism/ID candidate genesets.
Enrichment test empirical P-values for the secondary (autism/ID) geneset. As in Table 2, the top panel shows uncorrected P-values; tests significant after multiple test correction are in bold (i.e. all Pcorrected >0.05). Because no class of variant is significant after multiple test correction for the omnibus test (top panel), we applied and corrected for all 108 tests (9 conditions by 12 subsets) in the lower panel. The single category FMRP targets (Darnell et al.) mainly reflects disruptive and NSstrict singleton enrichment.
| Variant type | Geneset/subset | N genes | Singletons | MAF < 0.1% | MAF < 0.5% |
|---|---|---|---|---|---|
| Disruptive | 0.029 | 0.043 | 0.049 | ||
| Nonsyn (strict) | Autism/ID | 2,507 | 0.052 | 0.008 | 0.013 |
| Nonsyn (broad) | 0.532 | 0.619 | 0.287 | ||
|
| |||||
| N genes | Min. pcorrected (for 9×12=108 tests) | ||||
| Disruptive, nonsyn(strict), & nonsyn(broad) | De novo genes (exome sequencing) | ||||
| Autism (disruptive) | 128 | 1.000 | |||
| Autism (nonsyn) | 743 | 1.000 | |||
| ID (disruptive) | 30 | 0.070 | |||
| ID (nonsyn) | 132 | 0.995 | |||
| Neurodevelopmental candidates | |||||
| Betancur (2011), ASD candidates | 112 | 1.000 | |||
| Betancur (2011), ID candidates | 196 | 1.000 | |||
| Autism PPI networks | |||||
| O’Roak et al (2012), CHD8 network | 6 | 1.000 | |||
| O’Roak et al (2011), 49-gene network | 49 | 1.000 | |||
| O’Roak et al (2012), 74-gene network | 74 | 1.000 | |||
| Fragile × mental retardation protein targets | |||||
| Darnell et al. (2012) targets | 788 | 0.010 | |||
| Ascano et al. (2012) targets | 939 | 0.997 | |||
| Ascano et al. (2012) FMRP/autism overlap | 93 | 0.993 | |||