Table 1 Prioritized schizophrenia genes from common and rare variant studies.
a. PGC GWAS of Common SNPs (76,755 cases and 243,649 controls, ref. [20])* | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene Symbol | Ensembl gene ID | Chromosome | Gene biotype | Index SNP ID | Position (hg19) | Ref | Alt | Uncorrected P value | Control frequency | PGC odds ratio (95% CI) | Prioritized by fine mapping | Prioritized by Mendelian randomization | SCHEMA uncorrected P value | SCHEMA odds ratio** (95% CI) |
CUL9 | ENSG00000112659 | 6 | protein_coding | rs113113059 | 43160375 | T | C | 2.29E-11 | 0.756 | 1.06 (1.04-1.08) | Yes | Yes | 0.548 | 1.03 (0.436–2.19) |
FURIN | ENSG00000140564 | 15 | protein_coding | rs4702 | 91426560 | G | A | 2.15E-23 | 0.446 | 1.08 (1.07-1.10) | Yes | Yes | 0.066 | 2.68 (0.555–11.3) |
GRIN2A | ENSG00000183454 | 16 | protein_coding | rs9926049 | 9939960 | C | A | 3.16E-10 | 0.736 | 0.95 (0.93-0.96) | Yes | No | 7.37E-07†| 24.1 (5.36-221) |
LINC00320 | ENSG00000224924 | 21 | lincRNA | rs459391 | 22120508 | T | C | 1.54E-08 | 0.185 | 1.06 (1.04-1.08) | Yes | Yes | NA | NA |
SNAP91 | ENSG00000065609 | 6 | protein_coding | rs2022265 | 84293271 | A | G | 3.74E-10 | 0.523 | 1.05 (1.03-1.07) | Yes | Yes | 1 | 0 (0–6.08) |
SP4 | ENSG00000105866 | 7 | protein_coding | rs7811417 | 21534152 | T | C | 2.17E-09 | 0.347 | 1.05 (1.03-1.07) | Yes | No | 5.08E-07†| 7.59 (3.2-19.3) |
ZNF823 | ENSG00000197933 | 19 | protein_coding | rs72986630 | 11849736 | C | T | 3.07E-10 | 0.939 | 0.89 (0.86-0.93) | Yes | Yes | 0.438 | 1.38 (0.602–2.92) |
b. SCHEMA study of rare SNVs/indels (24,248 cases, 97,322 controls, and 3,402 case trios, ref. [21]) | Â | Â | Â | Â | Â | Â | Â | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene Symbol | Ensembl gene ID | Chromosome | Case LOF/PTV count | Control LOF/PTV count | Case missense (MPC ≥ 3) count | Control missense (MPC ≥ 3) count | De novo LOF/PTV count | Uncorrected P | Bonferroni | Odds ratio* (95% CI) | OMIM gene ID | OMIM phenotype |
SETD1A | ENSG00000099381 | 16 | 15 | 3 | 3 | 4 | 3 | 2.00E-12 | 4.66E-08 | 10.3 (4.12-29.3) | 611052 | Neurodevelopmental disorder with speech impairment and dysmorphic facies |
CUL1 | ENSG00000055130 | 7 | 8 | 1 | 2 | 0 | 3 | 2.01E-09 | 4.69E-05 | 44.2 (6.42-253) | 603134 | None |
XPO7 | ENSG00000130227 | 8 | 12 | 1 | 1 | 1 | 1 | 7.18E-09 | 0.000167 | 28.1 (6.46-253) | 606140 | None |
TRIO | ENSG00000038382 | 5 | 18 | 16 | 0 | 0 | 2 | 6.35E-08 | 0.001481 | 5.02 (2.47-10.4) | 601893 | Intellectual developmental disorder, autosomal dominant, with microcephaly |
CACNA1G | ENSG00000006283 | 17 | 10 | 13 | 8 | 4 | 0 | 4.57E-07 | 0.010658 | 4.25 (2.07-8.78) | 604065 | Spinocerebellar ataxia, early-onset, severe, with neurodevelopmental deficits |
SP4 | ENSG00000105866 | 7 | 13 | 6 | 3 | 3 | 1 | 5.08E-07 | 0.011847 | 7.59 (3.2-19.3) | 600540 | None |
GRIA3 | ENSG00000125675 | X | 5 | 0 | 3 | 2 | 1 | 5.98E-07 | 0.013946 | 20.1 (4.28-188) | 305915 | Intellectual developmental disorder, X-linked, syndromic, Wu type |
GRIN2A | ENSG00000183454 | 16 | 9 | 2 | 3 | 0 | 0 | 7.37E-07 | 0.017188 | 24.1 (5.36-221) | 138253 | Epilepsy, focal, with speech disorder and with or without impaired intellectual development |
HERC1 | ENSG00000103657 | 15 | 28 | 32 | 0 | 0 | 0 | 1.26E-06 | 0.029384 | 3.51 (2.04-6.03) | 605109 | None |
RB1CC1 | ENSG00000023287 | 8 | 9 | 4 | 0 | 0 | 2 | 0.000002 | 0.046642 | 10 (2.89-43.9) | 606837 | None |
c. PGC CNV Working Group study (21,094 cases and 20,227 controls, ref. [31]) | Â | Â | Â | Â | Â | ||||
|---|---|---|---|---|---|---|---|---|---|
Locus (gene) | Chromosome | Start (hg18) | End (hg18) | CNV type | Case count | Control count | Regional uncorrected P value | Odds ratio (95% CI) | Contained genes |
22q11.21 | 22 | 17400000 | 19750000 | Loss | 64 | 1 | 5.70E-18 | 67.7 (9.3-492.8) | DGCR2, AC004471.2, TSSK2, DGCR14, GSC2, SLC25A1, CLTCL1, HIRA, MRPL40, C22orf39, UFD1L, CDC45L, CLDN5, SEPT5, GP1BB, TBX1, GNB1L, C22orf29, TXNRD2, COMT, ARVCF, C22orf25, DGCR8, HTF9C, RANBP1, ZDHHC8, RTN4R, DGCR6L, AC007663.29, AC023490.5-2, GGTLC3, TMEM191C, PI4KAP1, RIMBP3, AC011718.2, AC007731.16-3, AC007731.16-4, USP41, ZNF74, SCARF2, KLHL22, MED15, POM121L4P, PI4KA, SERPIND1, SNAP29, CRKL, AC002470.17-2, AIFM3, LZTR1, THAP7, AC002472.8-1, P2RX6, SLC7A4, P2RX6P, AC002472.8-2 |
16p11.2, proximal | 16 | 29560000 | 30110000 | Gain | 70 | 7 | 2.52E-12 | 9.4 (4.2-20.9) | SPN, QPRT, C16orf54, AC009133.7-1, KIF22, MAZ, PRRT2, C16orf53, MVP, CDIPT, AC120114.2-2, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, AC093512.2, FAM57B, ALDOA, PPP4C, TBX6, YPEL3, GDPD3, MAPK3, CORO1A, BOLA2B, ZNF688, ZNF688 |
2p16.3 (NRXN1) | 2 | 50000992 | 51113178 | Loss | 35 | 3 | 4.92E-09 | 14.4 (4.2-46.9) | NRXN1 |
15q13.3 | 15 | 28920000 | 30270000 | Loss | 28 | 2 | 2.13E-07 | 15.6 (3.7-66.5) | MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, CHRNA7 |
1q21.1 | 1 | 144646000 | 146176000 | Loss + gain | 60 | 14 | 1.50E-06 | 3.8 (2.1-6.9) | PDZK1P2, PDZK1P2, NBPF8, NBPF8, FAM108A3, AL049742.8-2, NBPF12, PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, GPR89B, PDZK1P2, NBPF11, NBPF11, FAM108A2, FAM108A2, BX842679.19 |
3q29 | 3 | 197230000 | 198840000 | Loss | 16 | 0 | 1.86E-06 | Infinity | TFRC, ZDHHC19, AC069257.28-2, PCYT1A, TM4SF19, TCTEX1D2, UBXN7, C3orf43, RNF168, FBXO45, WDR53, C3orf34, LRRC33, PIGX, PAK2, SENP5, NCBP2, PIGZ, MFI2, DLG1, BDH1 |
16p11.2, distal | 16 | 28730000 | 28960000 | Loss | 11 | 1 | 5.52E-05 | 20.6 (2.6-162.2) | ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, LAT, AC112166.3-2 |
7q11.23 | 7 | 72380000 | 73780000 | Gain | 16 | 1 | 0.000168 | 16.1 (3.1-125.7) | TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, WBSCR22, STX1A, ABHD11, CLDN3, AC093168.3, CLDN4, WBSCR27, WBSCR28, ELN, LIMK1, WBSCR1, LAT2, RFC2, CYLN2, GTF2IRD1, GTF2I |
