Table 1.
Exome-wide, gene-based, PTV burden association-identified genes for EDU, RT and VNR in EUR samples in the UKB
| Gene symbol | Associated phenotype(s) | EDU | RT | VNR | Known gene–phenotype relationships | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| β (95% CI) | P | n PTV carrier | β (95% CI) | P | n PTV carrier | β (95% CI) | P | n PTV carrier | |||
| ADGRB2 | EDUa | −0.664 (−0.854 to −0.473) | 8.55 × 10−12 | 71 | 0.159 (−0.070 to 0.388) | 0.174 | 70 | −0.615 (−0.976 to −0.255) | 8.28 × 10−4 | 25 | |
| KDM5B | EDUa/RTa/VNRa | −0.307 (−0.419 to −0.195) | 8.68 × 10−8 | 204 | 0.447 (0.311 to 0.582) | 9.60 × 10−11 | 201 | −0.547 (−0.750 to −0.344) | 1.24 × 10−7 | 79 | MIM: autosomal recessive intellectual developmental disorder-65 |
| Exome study: DD, ASD | |||||||||||
| GIGYF1 | EDUa | −0.492 (−0.660 to −0.324) | 9.80 × 10−9 | 91 | 0.275 (0.076 to 0.473) | 6.78 × 10−3 | 93 | −0.490 (−0.771 to −0.209) | 6.43 × 10−4 | 41 | Exome study: DD, ASD |
| ANKRD12 | VNRa/EDUb | −0.310 (−0.445 to −0.176) | 6.26 × 10−6 | 142 | 0.101 (−0.057 to 0.260) | 0.210 | 146 | −0.694 (−0.941 to −0.447) | 3.77 × 10−8 | 53 | Exome study: SCZ |
| SLC8A1 | EDUa | −0.992 (−1.371 to −0.613) | 2.84 × 10−7 | 18 | 0.202 (−0.250 to 0.654) | 0.381 | 18 | NA | NA | 4 | |
| RC3H2 | VNRa | −0.337 (−0.612 to −0.062) | 0.016 | 34 | 0.132 (−0.196 to 0.461) | 0.430 | 34 | −1.126 (−1.576 to −0.676) | 9.32 × 10−7 | 16 | |
| CACNA1A | VNRa | −0.210 (−0.391 to −0.029) | 0.023 | 78 | 0.352 (0.129 to 0.575) | 1.95 × 10−3 | 74 | −0.824 (−1.159 to −0.490) | 1.33 × 10−6 | 29 | MIM: spinocerebellar ataxia-6; type 2 episodic ataxia; familial hemiplegic migraine-1; developmental and epileptic encephalopathy-42. Exome study: DD |
| BCAS3 | EDU | −0.419 (−0.592 to −0.246) | 1.99 × 10−6 | 86 | 0.207 (−0.003 to 0.417) | 0.054 | 83 | −0.361 (−0.670 to −0.053) | 0.022 | 34 | MIM: Hengel–Maroofian–Schols syndrome |
The sample sizes, number of genes tested and λGC for each phenotype are as follows: nsample = 393,758, ntest = 15,782 and λGC = 0.967 for EDU; nsample = 394,600, ntest = 15,798 and λGC = 0.961 for RT; and nsample = 159,026, ntest = 11,905 and λGC = 0.959 for VNR. We excluded genes with fewer than ten PTV carriers from the analysis. The ‘associated phenotype(s)’ column indicates the phenotype for each gene with Bonferroni significance (adjusted by ntest for each phenotype). aIndicates genes that showed exome-wide significant association (bold) after Bonferroni correction across all tests (two-sided t-test: P < 0.05/43,485 = 1.15 × 10−6). bFDR was significant for EDU. β values represent rank-based inverse-normal transformed phenotypes and correspond to s.d. change in the phenotype. The table was sorted according to the lowest P value across three phenotypes.