Extended Data Table 3. Genes prioritized as more likely to harbor large-effect alleles.
Individual gene case/control counts, odds ratios and P-values for genes from primary genesets with odds ratios > 5, and KYNU (top-ranked individual gene). Odds ratios are calculated using Firth’s method (penalized maximum likelihood logistic regression) and shown with 95% confidence intervals. P-values are empirical, uncorrected one-sided burden tests. FMRP target annotations are based on the Darnell et al. list only. Supplementary Table S1 lists singleton variant and genotype information for the genes listed here.
| Class | Gene | Singletons | MAF < 0.1% | Notes |
|---|---|---|---|---|
| ARC/PSD complex | ||||
| CYFIP1 | 1/0 | 1/0 | SCZ de novo (CNV) | |
| BAIAP2 | 1/0 | 1/0 | SCZ de novo (NS) | |
| DLG1 | 1/0 | 1/0 | SCZ de novo (NS), SCZ de novo (CNV) | |
| SLC25A3 | 1/0 | 1/0 | ||
| GLUD1 | 1/0 | 1/0 | ||
| CAMK2A | 1/0 | 1/0 | FMRP target | |
| ATP1B1 | 1/0 | 1/0 | AUT de novo (disruptive); FMRP target | |
| IQSEC2 | 1/0 | 1/0 | ID de novo (disruptive); FMRP target | |
| MBP | 1/0 | 1/0 | FMRP target | |
| Total | 9/0 | 9/0 | ||
| P = 0.0016 | P = 0.0014 | |||
| OR = 19.2 (2.4 - 2471) | OR = 19.2 (2.4 - 2471) | |||
| PSD-95 genes | ||||
| ABLIM1 | 1/0 | 1/0 | ||
| ACO2 | 1/0 | 1/0 | FMRP target | |
| ANKS1B | 3/1 | 3/1 | ||
| ATP1B1 | 1/0 | 1/0 | AUT de novo (disruptive); FMRP target | |
| ATP5A1 | 1/0 | 1/0 | FMRP target | |
| BAIAP2 | 1/0 | 1/0 | SCZ de novo (NS) | |
| CAMK2A | 1/0 | 1/0 | FMRP target | |
| CAMK2B | 2/0 | 2/0 | FMRP target | |
| DLG1 | 1/0 | 1/0 | SCZ de novo (NS), SCZ de novo (CNV) | |
| GAPDH | 1/0 | 1/0 | ||
| IQSEC2 | 1/0 | 1/0 | ID de novo (disruptive); FMRP target | |
| NRXN1 | 1/0 | 1/0 | SCZ de novo (NS); AUT de novo (disruptive); FMRP target | |
| PRDX1 | 0/1 | 0/1 | ||
| PRDX2 | 0/1 | 0/1 | ||
| SUCLA2 | 1/0 | 1/0 | AUT de novo (disruptive) | |
| SYNGAP1 | 1/0 | 1/0 | SCZ de novo (disruptive); ID de novo (disruptive); FMRP target | |
| Total | 17/3 | 17/3 | ||
| P = 0.0017 | P = 0.0009 | |||
| OR = 5.1 (1.8 - 19.2) | OR = 5.1 (1.8 - 19.2) | |||
| Voltage-gated calcium ion channel genes | ||||
| CACNA1B | 1/0 | 1/0 | FMRP target | |
| CACNA1C | 2/0 | 2/0 | SCZ & BP GWAS hit | |
| CACNA1H | 1/0 | 3/0 | ||
| CACNA1S | 2/0 | 2/3 | SCZ & AUT de novos (NS) | |
| CACNA2D1 | 1/0 | 1/0 | PSD | |
| CACNA2D2 | 3/0 | 3/0 | ||
| CACNA2D3 | 0/0 | 3/0 | AUT de novo (disruptive) | |
| CACNA2D4 | 1/0 | 2/4 | ||
| CACNB2 | 0/1 | 0/1 | ||
| CACNB4 | 1/0 | 1/0 | PSD | |
| Total | 12/1 | 15/8 | ||
| P = 0.0021 | P = 0.021 | |||
| OR = 8.4 (2.03 - 77) | OR = 2.1 (0.97 - 4.9) | |||
| Top disruptive gene-based test | ||||
| KYNU | 3/0 | 10/0 | ||
| P = 0.13 | P = 0.0017 | |||
| OR = 21.2 (2.7 - 2725) | ||||