Table 2.
Recurrent SNV, CNV, de novo and likely gene-disruptive variations, found at least twice per gene
| Gene | ExAC (z-score) | PED (N) | N variants (type) | N aff (unaff) relatives | PGC1-BD VEGAS P | PGC2-SCZ VEGAS P |
|---|---|---|---|---|---|---|
| ANGPTL5 NB | −1.85 | 2 | 1 SNV (mis) | 6 (2) | 0.045 | 0.863 |
| DGCR5 | ND | 2 | 2 CNVs (dup, del) | 8 (2) | 0.611 | 0.125 |
| DNAH14 NB | −0.68 | 1 | 2 SNVs (fs) | 4 (1) | 0.201 | 0.338 |
| FAT2 | −1.01 | 2 | 2 SNVs (mis) | 6 (2) | 0.791 | 0.22 |
| HECTD4 | 6.77 | 2 | 2 SNVs (mis) | 7 (1) | 0.367 | 0.146 |
| HYDIN | ND | 3 | 2 SNVs (mis) | 9 (2) | 0.651 | 0.009 |
| KIAA1731 | −0.18 | 2 | 2 SNVs (mis) | 8 (1) | 0.654 | 0.955 |
| MAP4 | −0.94 | 3 | 1 SNV (mis); 1 DN (mis) | 5 (1) | 0.61 | 0.032 |
| MIA3 | −1.43 | 2 | 2 SNVs (mis) | 6 (0) | 0.111 | 0.027 |
| MUC5B NB | 6.3 | 5 | 6 SNVs (mis) | 10 (8) | 0.254 | 0.08 |
| NEB NB | −3.74 | 3 | 4 SNVs (mis) | 9 (3) | 0.098 | 0.033 |
| NRG1 | 0.62 | 2 | 2 SNVs (mis) | 6 (1) | 0.232 | 0.47 |
| OBSCN | −1.17 | 2 | 2 SNVs (mis) | 6 (2) | 0.947 | 0.289 |
| PCDHA8 | 2.24 | 3 | 3 CNVs (del) | 9 (1) | 0.022 | 6.10E-05 |
| PCDHA9 | 2.28 | 3 | 3 CNVs (del) | 9 (1) | 0.02 | 7.20E-05 |
| PCDHA10 | 1.2 | 2 | 2 CNVs (del) | 7 (1) | 0.023 | 8.30E-05 |
| PCDH15 | −2.88 | 3 | 3 SNVs (mis) | 9 (2) | 0.101 | 0.042 |
| PRODH | 0.77 | 2 | 1 SNV; 2 CNVs (dup, del) | 9 (3) | 0.934 | 0.451 |
| PRUNE2 | −1.48 | 2 | 2 SNVs (mis) | 7 (0) | 0.427 | 0.728 |
| SCN10A NB | −1.8 | 2 | 4 SNVs (mis) | 7 (4) | 0.291 | 0.089 |
| SETX | −1.62 | 2 | 2 SNVs (mis) | 8 (1) | 0.085 | 0.479 |
| SLC5A10 | 0.23 | 1 | 2 SNVs (mis) | 3 (1) | 0.061 | 0.002 |
| SOGA1 | 2.17 | 2 | 2 SNVs (mis) | 7 (1) | 0.358 | 0.089 |
| TNC | −0.12 | 3 | 3 SNVs (mis) | 8 (3) | 0.367 | 0.055 |
| TTN NB | −4.93 | 7 | 13 SNVs (mis) | 19 (7) | 0.014 | 0.16 |
| VMAC | 0.81 | 2 | 2 SNVs (mis) | 7 (1) | 0.002 | 0.32 |
| XDH NB | −2.01 | 2 | 2 SNVs (mis) | 6 (0) | 0.466 | 0.434 |
| ZNF506 | 0.09 | 2 | 2 SNVs (mis, fs) | 6 (1) | 0.43 | 0.221 |
| ZNF812 NB | −4.76 | 2 | 2 SNVs (mis, fs) | 7 (1) | 0.851 | 0.639 |
For each gene, a measure of functional constraint in the form of ExAC missense z-score36 is provided. The number of pedigrees (PED N) with converging evidence for each gene is given, along with the number and type of variant identified (SNV single-nucleotide variant, CNV copy number variant, DN de novo variant, mis missense, fs frameshift, dup duplication, del deletion). The total number of affected relatives (N aff) and total number of unaffected relatives (N unaff) who carry a variant in the gene are indicated. Evidence of gene-level association with BD and schizophrenia was derived from summary statistics from Psychiatric Genomics Consortium GWAS6,37 with VEGAS2, where p-values < 0.05 are indicated in bold text. Postsynaptic density (PSD) gene names33 are indicated in bold. NB, genes with negligible expression in the brain (RPKM < 1 in developmental transcriptomics RNA-seq data; http://www.brainspan.org/rnaseq/search/index.html). Further information on variants described above is reported in Supplementary Table S1, S2 and S3