Table 1. Overview of genes in GW analyses meeting the significance criteria and relationships with functional clusters (symbols highlighted in bold) mentioned in the Results section.
| sI | sII | sF | Symbol | Synonym | Entrez | Gene name (some shortened to fit) | Function (selected from Entrez/UniProtKB/Swiss-Prot/TOCRIS) | |
|---|---|---|---|---|---|---|---|---|
| (a) Genes above the projected apex in ssGWAS (μGWAS P-values shown) | ||||||||
| 6.96 | 6.21 | ANO4a | TMEM16D | 121601 | Anoctamin 4 | Ca2+-activated Cl− channel (CaCC) | ||
| 6.19b | ANO2a | TMEM16B | 57101 | Anoctamin 2 | Ca2+-activated Cl− channel (CaCC) | |||
| 6.94 | 3.76 | 9.29 | DOK5 | 55816 | Docking protein 5 | Interacts with phosphorylated receptor tyrosine kinases | ||
| 5.76 | NTMT1 | METTL11A | 28989 | N-methyltransferase 1 | Methylates protein targets such as SET and RB | |||
| (b) Genes above the estimated apex in μGWAS | ||||||||
| 6.81 | MMP10 | Stromelysin 2 | 4319 | Matrix metallopeptidase 10 | Degrades proteoglycans and fibronectin | |||
| 6.73 | PDGFB | 5155 | Platelet-derived GF β | Initiating signaling through the MAPK, PI3K and PKCγ pathways | ||||
| 6.64 | MRGPRX2 | 117194 | MAS-related GPR, mbr X2 | GqPR mediating cortistatin-stimulated increases in intracellular Ca2+ | ||||
| 6.63 | SGMS1 | TMEM23 | 259230 | Sphingomyelin synthase 1 | Large, zinc-finger-containing transcription factor | |||
| 6.62 | GRIK5 | 2901 | Glutamate receptor, ionotropic, kainate | Excitatory neurotransmitter in the CNS | ||||
| 6.59 | SMAP2 | 64744 | Small ArfGAP2 | Stromal GTPase-activating protein (GAP) that acts on ARF1 | ||||
| 6.55 | FAM13A | ARHGAP48 | 10144 | Fam with sequence similarity 13, mbr A | Rho GTPase activating protein | |||
| 6.44 | 4.84 | 9.85 | SORCS2 | 57537 | Sortilin-related receptor 2 | Containing VPS10 domain | ||
| 6.38 | 4.20 | 9.17 | PPFIBP1c | 8496 | Liprin Beta 1 | PTPRF interacting protein, binding protein 1 | ||
| 6.98 | KCNMA1 | Kca1.1 | 3778 | Maxi-K Ca2+-activated channel | Large conductance channel that dampens excitatory events | |||
| 6.23 | HTR1B | 5-HT1B | 3351 | Serotonin receptor 1B | G-protein-coupled receptor involved in neuropsychiatric disorders | |||
| (c) Genes among the top 100 genes in μGWAS in both stages (in addition to SORCS2) | ||||||||
| 5.27 | 4.99 | 8.86 | CDH13 | H-cadherin | 1012 | Cadherin 13 | Downregulates axon growth during neural differentiation | |
| 5.02 | 5.15 | 8.78 | PGR | NR3C3 | 5241 | Progesteron receptor | Nuclear/membrane36 hormone receptor | |
| 5.42 | 4.64 | 8.68 | GRK5 | 2869 | GPR kinase 5 | Phosphorylates the activated forms of GPRs | ||
| 5.43 | 4.51 | 8.56 | PZP | 5858 | Pregnancy-zone protein | Inhibits all four classes of proteinases | ||
| 4.89 | 5.07 | 8.57 | PTPRTc | 11122 | PTP, receptor type, T | May be involved in signal transduction and cellular adhesion in the CNS | ||
| (d) Additional genes jointly (Fisher) above the joined projected apex in μGWAS (in addition to KCNMA1) | ||||||||
| 4.81 | 5.81 | 9.22 | HIVEP2 | Schnurri-2 | 3097 | MHC binding protein 2 | ||
| 4.74 | 5.66 | 9.01 | SEPT9 | 10801 | Septin 9 | Filament-forming cytoskeletal GTPase | ||
| 5.85 | 4.52 | 8.97 | DMD | 1756 | Dystrophin | Ligand for dystroglycan | ||
| 5.61 | 4.44 | 8.66 | SHROOM3 | APXL3 | 57619 | F-actin-binding protein | Controls cell shape changes during neural tube closure | |
| (e) Genes related to PTPRs among the top 100 genes in μGWAS in at least one stage (in addition to PPFIBP1 and PTPRT) | ||||||||
| 5.64 | 3.47 | 7.77 | PTPRB | 9665 | PTP, receptor type, B | Interacts with neuronal receptor, contactin and tenascin C | ||
| 4.05 | 4.53 | 7.26 | PTPRD | 5789 | PTP, receptor type, D | Interacts with IL1RAPL1 for synapse formation | ||
| 5.47 | IL1RAPL2 | 26280 | IL-1 receptor accessory protein-like 2 | Closely related to IL1RAPL1 | ||||
| 5.39 | CNTN6 | NB-3 | 27255 | Contactin 6 | Mediates cell surface interactions during NS development | |||
| 4.93 | CNTNAP2 | AUTS15 | 26047 | Contactin-associated protein-like 2 | Mediates neuron–glia interactions during NS development | |||
| 4.58 | CNTN4 | BIG-2 | 152330 | Contactin 4 | May have a role in the formation of axon connections | |||
| 4.68 | ERC2 | 26059 | ELKS/RAB6-interacting/CAST fam mbr 2 | May recruit liprin-alpha proteins to the nerve terminals active zone | ||||
| (f) Genes related to Cl−signaling among the top 100 genes in μGWAS in at least one stage (in addition to ANO4) | ||||||||
| 5.05 | CLCN7 | PPP1R63 | 1186 | Chloride channel, voltage-sensitive 7 | H+/Cl− exchange transporter 7 | |||
| 4.65 | CAMK2A | 815 | CaM dependent kinase II alpha | Mediates many of the second messenger effects of Ca2+ | ||||
| 4.67 | LRRC7 | Densin-180 | 57554 | Leucine-rich repeat containing 7 | Necessary for DISC1 and GRM5 localization to PSD complexes | |||
Abbreviations: Cam, calcium/calmodulin; fam, family; GF, growth factor; GPR, G-protein-coupled receptor; mbr, member; PTP, protein tyrosine phosphatase.
a
Genes related to section (f).
b
From comparison of HFA cases vs all parental controls, Figure 4.
c
Genes related to section (e).