Table 5.
Top significantly enriched categories (LogP value < −4) with variants associated with Tourette syndrome
| Term ID | Description | LogP | Genes in which variants were found | MAF below, %* |
|---|---|---|---|---|
| GO:0098609 | Cell-cell adhesion | −13.56 | CDH23†‡, NLGN1†, PTPRT†, ROBO2†‡, ADGRL3‡, CD44, CLSTN2, CNTN4‡, CTNNA3, FN1‡, GNAS, LPP, NRXN3, PKHD1‡, PKP4, PTPRD, SDK1‡, TENM2‡ | 5.0 |
| GO:0000902 | Cell morphogenesis | −7.93 | CDH23†‡, EPHB1†, NLGN1†, ROBO2†‡, SEMA3A†‡, AUTS2, CNTN4‡, FN1‡, NCAM1‡, NRG1, NRXN3, PKHD1‡, PLXNC1‡, USH2A‡ | 5.0 |
| GO:0034329 | Cell junction assembly | −7.75 | ERBB4, BSN‡, PKP4†, PTPRD†, ADGRL3‡, NRXN1, CDH22, EPB41L3‡, FN1‡, CLDN14 | 0.1 |
| GO:0034330 | Cell junction organization | −7.70 | EPHB1†, NLGN1†, ADGRL3‡, DLC1‡, ERBB4, ERC2, FN1‡, NRG1, PKHD1‡, PKP4, PTPRD, SDK1‡ | 5.0 |
| GO:0098609 | Cell-cell adhesion | −7.57 | TENM2, CDH22, CDH23‡, CNTN4‡, ROBO2†‡, PTPRD†, ADGRL3‡, CLDN14, PIK3CG, NRXN1, NRXN3, PKP4†, FN1‡ | 0.1 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | −6.94 | KCNMA1, EPB41L3‡, CDH23‡, CACNA2D2‡, BSN‡, SLC17A8‡ | 0.1 |
| GO:0007420 | Brain development | −6.77 | SATB2, ERBB4, MEIS2, RARB, ROBO2†‡, ALK‡, PRKG1†, CDH22, NDRG2‡, ADGRL3‡, EPHB1, ZNF148, SLC17A8‡, CNTN4‡ | 0.1 |
| GO:0016358 | Dendrite | −6.56 | CACNA1C†, EPHB1†, NLGN1†, SEMA3A†‡, ANKS1B, CLSTN2, GIGYF2‡, KCNIP4, MAGI2, SLC4A10, SLC8A1, TENM2‡ | 5.0 |
| GO:0007420 | Brain development | −6.50 | EPHB1†, ROBO2†‡, SEMA3A†‡, MACROD2†, ADGRL2, ADGRL3‡, CNTN4‡, DLC1‡, ERBB4, NRG1, PLCB1, RARB, SLC4A10, SLC8A1 | 5.0 |
| GO:0008038 | Neuron recognition | −6.44 | OPCML†, ROBO2†‡, NTM†, CNTN4‡ | 5.0 |
| GO:0030424 | Axon | −6.41 | EPHB†, ROBO2†‡, SEMA3A†‡, ADGRL3‡, AUTS2, CNTN4‡, ERC2, NRG1, SLC4A10, SLC8A1, TENM2‡, USH2A‡ | 5.0 |
| GO:0000902 | Cell morphogenesis | −6.06 | CDH22, CDH23†‡, EPHB1, KLF7, NLGN1, NRXN3, NTN4, PLXNC2‡, ROBO2†‡, SEMA3A†‡ | 1.0 |
| GO:0098609 | Cell-cell adhesion | −5.90 | CDH22, CDH23†, GNAS†, NLGN1, NRXN3, PKP4, PTPRD, ROBO2†‡, TENM2†‡ | 1.0 |
| GO:0051963 | Regulation of synapse assembly | −5.90 | NRXN1, EPHB1, SEMA4A‡, ROBO2†‡, PTPRD†, COLQ | 0.1 |
| GO:0007626 | Locomotory behaviour | −5.85 | BTBD9†, CDH23†‡, FGF12, GIGYF2‡, NAV2‡, NRG1, SLC4A10 | 5.0 |
| GO:0005509 | Calcium ion binding | −5.85 | CDH23†‡, EYS†, ADGRL3‡, CLSTN2, FSTL5, KCNIP4, LTBP1‡, PLCB1, SLC8A1, STAB2‡, TENM2‡, TLL2‡ | 5.0 |
| GO:0040007 | Growth | −5.75 | EYS†, SEMA3A†‡, AUTS2, ERBB4, GIGYF2‡, GNAS, MAGI2, RARB, SLC4A10 | 5.0 |
| GO:0007167 | Enzyme-linked receptor protein signalling pathway | −5.72 | EPHB1†, PTPRT†, ANKS1B, ERBB4, FGF12, GIGYF2‡, LTBP1‡, MAGI2, NRG1, PLCB1, PTPRD | 5.0 |
| GO:0007420 | Brain development | −5.65 | ADGRL2, ALK‡, CDH22, EPHB1, ERBB4, MACROD2†, PRKG1, RARB†, ROBO2†‡, SEMA3A†‡, SRGAP2C | 1.0 |
| GO:0051962 | Positive regulation of nervous system development | −5.47 | FN1‡, SEMA4A‡, MAP3K13, ROBO2†‡, PLXNC1‡, PTPRD†, EPHB1, NRXN1 | 0.1 |
| GO:0120035 | Regulation of plasma membrane bounded cell projection organization | −5.36 | ALK‡, NLGN1, PLCE1‡, PLXNC1‡, PTPRD, ROBO2†‡, SEMA3A†‡, SRGAP2C, TENM2†‡ | 1.0 |
| GO:0098858 | Actin-based cell projection | −5.34 | CDH23†‡, EPHB1†, NLGN1†, CD44, IQGAP2‡, TENM2‡, USH2A‡ | 5.0 |
| GO:0034330 | Cell junction organization | −5.27 | CDH22, EPHB1, ERBB4, ERC2, NLGN1, PKP4, PTPRD, SRGAP2C | 1.0 |
| GO:0050804 | Modulation of chemical synaptic transmission | −5.21 | BTBD9†, EPHB1†, NLGN1†, CLSTN2, CNTN4‡, ERC2, PLCB1, PTPRD, SLC4A10 | 5.0 |
| GO:0016324 | Apical plasma membrane | −4.89 | KCNMA1†‡, CD44, FN1‡, GNAS, PARD3B, PKHD1‡, SLC4A10, USH2A‡ | 5.0 |
| GO:0005539 | Glycosaminoglycan binding | −4.89 | COL25A1†, CD44, FN1‡, HK1‡, NAV2‡, STAB2‡ | 5.0 |
| GO:0050885 | Neuromuscular process controlling balance | −4.67 | NRXN1, RBFOX1, CAMTA1, CDH23 ‡ | 0.1 |
| GO:0016358 | Dendrite development | −4.16 | EPHB1, KLF7, PRKG1, SEMA3A † ‡ | 1.0 |
| GO:0045932 | Negative regulation of muscle contraction | −4.11 | PRKG1†, KCNMA1, PIK3CDG | 0.1 |
| WP2118 | Arrhythmogenic right ventricular cardiomyopathy | −4.10 | CACNA1C†, CACNA2D3†, CTNNA3, SLC8A1 | 5.0 |
| GO:0098858 | Actin-based cell projection | −4.07 | CDH23†, EPHB1, NLGN1, TENM†‡, WWOX | 1.0 |
| GO:0043408 | Regulation of MAPK cascade | −4.01 | EPHB1, ERBB4, ALK‡, MAP3K13, PIK3CG, FN1‡, NDRG2‡, NLRP12‡, PLCE1‡, MAPKBP1‡ | 0.1 |
MAF = minor allele frequency.
*
Analyses were performed separately on gene sets with ultra-rare variants (MAF below 0.1%) occurring in at least 2 families, rare variants (MAF below 1%) occurring in at least 3 families, and uncommon variants (MAF below 5%) occurring in at least 4 families.
†
Genes with variants found in all patients in at least n + 1 families, where n is the threshold value selected for a given MAF (i.e., 2 for 0.1%, 3 for 1% and 4 for 5%) threshold.
‡
Genes with missense and/or splicing variants.