Table 1.
Genome-wide significant loci and prioritized genes
| Phenotype | Locus | New/ replication | Lead SNP (A1:A2) | Freq1 | Z score | P value | Genes | Total | Missense | TWAS | SMR | MAGMA | PoPS | Brain exp | Brain-coX | KO mouse | AED target | Monogenic |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All epilepsy | 2p16.1 | Replication | rs13032423 (A:G) | 0.53 | −7.04 | 1.85 × 10−12 | BCL11A | 5 | – | – | – | – | * | * | * | * | – | * |
| 2q24.3 | Replication | rs59237858 (T:C) | 0.23 | −6.89 | 5.75 × 10−12 | SCN1A | 8 | * | – | – | * | * | * | * | * | * | * | |
| 9q21.13 | New | rs4744696 (A:G) | 0.82 | −5.74 | 9.69 × 10−9 | RORB | 4 | – | – | – | – | * | * | * | * | – | – | |
| 10q24.32 | New | rs3740422 (C:G) | 0.33 | 6.04 | 1.52 × 10−9 | KCNIP2 | 3 | – | – | – | * | – | * | * | – | – | – | |
| GGE | 1q43 | New | rs876793 (T:C) | 0.67 | −5.95 | 2.64 × 10−9 | RYR2 | 4 | – | – | – | – | * | * | * | * | – | – |
| CHRM3 | 4 | – | – | – | – | – | * | * | * | * | – | |||||||
| 2p16.1 | Replication | rs11688767 (A:T) | 0.53 | 9.38 | 6.58 × 10−21 | BCL11A | 5 | – | – | – | – | * | * | * | * | – | * | |
| 2q12.1 | New | rs62151809 (T:C) | 0.43 | 6.77 | 1.28 × 10−11 | POU3F3 | 3 | – | – | – | – | * | * | – | * | – | – | |
| 2q24.3 | Replication | rs11890028 (T:G) | 0.72 | 5.63 | 1.73 × 10−8 | SCN1A | 8 | * | – | – | * | * | * | * | * | * | * | |
| 2q32.2 | Replication | rs6721964 (A:G) | 0.66 | −6.18 | 6.54 × 10−10 | GLS | 4 | – | – | – | – | – | * | * | * | – | * | |
| 3p22.3 | New | rs9861238 (A:G) | 0.41 | −6.42 | 1.33 × 10−10 | STAC | 2 | – | – | – | – | * | – | * | – | – | – | |
| 3p21.31 | New | rs739431 (A:G) | 0.84 | 6.23 | 4.82 × 10−10 | CACNA2D2 | 6 | – | – | – | * | – | * | * | * | * | * | |
| 4p15.1 | Replication | rs1463849 (A:G) | 0.59 | −6.59 | 4.38 × 10−11 | PCDH7 | 3 | – | – | – | * | * | – | * | – | – | – | |
| 5q22.3 | Replication | rs4596374 (T:C) | 0.55 | −6.98 | 2.91 × 10−12 | KCNN2 | 6 | – | – | – | * | * | * | * | * | – | * | |
| 5q31.2 | New | rs2905552 (C:G) | 0.48 | −6.33 | 2.49 × 10−10 | SPOCK1 | 5 | – | – | – | * | * | * | * | * | – | – | |
| 6q22.33 | Replication | rs13219424 (T:C) | 0.29 | −5.49 | 3.87 × 10−8 | PTPRK | 3 | – | – | – | – | * | – | * | * | – | – | |
| 7p14.1 | New | rs37276 (T:G) | 0.26 | −5.69 | 1.29 × 10−8 | SUGCT | 2 | – | * | – | – | * | – | – | – | – | – | |
| 9q21.32 | New | rs2780103 (T:C) | 0.26 | −6.93 | 4.34 × 10−12 | RMI1 | 5 | * | * | * | * | – | – | – | * | – | – | |
| 10q24.32 | New | rs11191156 (A:G) | 0.67 | −7.55 | 4.41 × 10−14 | KCNIP2 | 4 | – | – | – | * | * | * | * | – | – | – | |
| 12q13.13 | New | rs114131287 (A:T) | 0.02 | 5.83 | 5.46 × 10−9 | SCN8A | 6 | – | – | – | – | * | * | * | * | * | * | |
| 16p13.3 | New | rs62014006 (T:G) | 0.05 | 5.88 | 4.22 × 10−9 | RBFOX1 | 5 | – | – | – | * | * | * | * | * | – | – | |
| 17p13.1 | New | rs2585398 (A:C) | 0.53 | −6.37 | 1.84 × 10−10 | ARHGEF15 | 6 | * | * | * | * | – | – | * | * | – | – | |
| 17q21.32 | Replication | rs16955463 (T:G) | 0.25 | −5.97 | 2.30 × 10−9 | CDK5RAP3 | 4 | – | * | * | * | – | – | – | * | – | – | |
| 19p13.3 | New | rs75483641 (T:C) | 0.14 | −6.22 | 4.85 × 10−10 | AP3D1 | 5 | * | – | * | * | – | – | – | * | – | * | |
| 21q21.1 | New | rs1487946 (A:G) | 0.59 | 5.47 | 4.41 × 10−8 | TMPRSS15 | 1 | – | – | – | – | * | – | – | – | – | – | |
| 21q22.1 | Replication | rs7277479 (A:G) | 0.36 | −6.82 | 8.94 × 10−12 | GRIK1 | 4 | – | – | – | – | – | * | * | * | * | – | |
| 22q13.32 | New | rs469999 (A:G) | 0.31 | −6.32 | 2.65 × 10−10 | FAM19A5 | 2 | – | – | – | – | * | * | – | – | – | – | |
| CAE | 2p16.1 | Replication | rs12185644 (A:C) | 0.70 | −7.12 | 1.04 × 10−12 | BCL11A | 5 | – | – | – | – | * | * | * | * | – | * |
| JME | 4p12 | Replication | rs17537141 (T:C) | 0.851 | −5.47 | 4.62 × 10−8 | GABRA2 | 6 | – | – | – | * | – | * | * | * | * | * |
| 8q23.1 | New | rs3019359 (T:C) | 0.414 | −5.55 | 2.89 × 10−8 | RSPO2 | 3 | – | – | – | – | * | * | * | – | – | – | |
| TMEM74 | 3 | – | – | – | – | – | * | * | * | – | – | |||||||
| 16p11.2 | Replication | rs1046276 (T:C) | 0.353 | 6.19 | 6.05 × 10−10 | STX1B | 5 | – | – | – | * | – | * | * | * | – | * | |
| CACNA1I | 5 | – | – | – | – | – | * | * | * | * | * |
Genome-wide significant loci are annotated with details from the lead-SNP and prioritized genes. Loci were classified as new or replication according to the genome-wide significant results of previous GWAS publications. Genes were scored based on ten criteria/methods, after which the gene with the highest score in the locus was selected as the prioritized gene. Genomic coordinates for each locus (hg19) can be found in Supplementary Table 4. Two-tailed P values and z scores were obtained by fixed-effects meta-analysis weighted by effective sample sizes.
Total, number of satisfied criteria for gene prioritization; missense, the locus contains a missense variant in the gene; TWAS, significant transcriptome-wide association with the gene; SMR, significant summary-based Mendelian randomization association with the gene; MAGMA, significant genome-wide gene-based association; PoPS, gene prioritized by polygenic priority score; brain exp, the gene is preferentially expressed in brain tissue; brain-coX, the gene is prioritized as co-expressed with established epilepsy genes; KO mouse, knockout of the gene causes a neurological phenotype in mouse models; monogenic, the gene is a known cause of monogenic epilepsy.