Table 2.
Non-cognitive factor (NCF) meta-loci, biological and drug gene sets, and druggable gene targets
| Meta-locus ID | N LD segments | h2 | Length (MB) | Biological gene setsa | Druggable genesc | Drug-based gene setsb |
|---|---|---|---|---|---|---|
| 1 | 125 | 0.0271 | 196.85 |
GOBP appendage development GOBP cell–cell junction organization GOBP cell fate commitment |
PDPK1 AKT3 APH1A ARNT PIP5K1A SV2A IMPDH2 P4HTM EPHA5 ADORA2A ANGPT1 CACNA2D2 ESR1 GABRA2 GABRA4 GABRB1 GABRG1 GPX1 GRIN2B LAMB2 LAMC1 MAPT MST1R VEGFA | CIPROFLOXACINd |
| 2 | 208 | 0.0303 | 243.30 |
GOBP regulation of postsynaptic membrane potential GOBP intrinsic apoptotic signaling pathway GOBP sensory organ morphogenesis |
HRAS GABRA1 GABRG2 PDE4D RXRG CAMK2G EPHA6 PKN1 SLC6A1 TP53 BACE1 CIT KMT2A PTK2 TNIK NTRK2 CACNA1C CHRM1 CHRNB1 CSK DAPK2 DDO GABRA6 HDAC7 HIF1A KIT NCOR2 NT5E PDE7A SNAP25 TNNI3K | VALPROIC_ACIDd; POLYMYXINSd; LAMOTRIGINE; PROPOFOL; PURINE_DERIVATIVES |
| 3 | 135 | 0.0205 | 164.43 |
GOBP metal ion transport GOBP-positive regulation of intracellular transport GOBP regulation of transmembrane transport |
PLK1 PRKCB CHRM2 CACNA2D1 CASP1 CCND1 CDK13 CHRND CHRNG GRIN2D GSK3B HCRTR2 JAK2 MAG NFKB1 SIK3 | - |
| 4 | 123 | 0.0158 | 138.01 |
GOBP-negative regulation of intracellular signal transduction GOBP-positive regulation of intracellular signal transduction GOBP response to extracellular stimulus |
CHRNA3 CHRNB4 OPRM1 ABL2 NTRK3 CDK4 RXRA PRKD1 VAMP2 SLC6A9 AURKB BCHE CYP27B1 EPHA1 GPBAR1 GPR17 IL1A KCNN4 MAST1 MGMT OPRD1 PDE4B S1PR4 TNK2 | ANAKINRA |
| 5 | 113 | 0.0168 | 135.20 | GOBP regulation of peptidyl tyrosine phosphorylation | RPS6KA5 PRKCA HDAC2 HDAC1 MARK2 PPP3CA CHRNA2 DRD1 ESRRA GRM5 ITGB3 LMNA MAP3K11 MAP4K2 MUC1 PAK1 PDE5A PSEN1 PTK2B SCN4A VEGFB | SILVERd |
| 6 | 105 | 0.0146 | 128.79 | - | - | - |
| 7 | 210 | 0.0199 | 231.07 |
GOBP glucose metabolic process GOMF cation channel activity |
CHRNB2 CACNA1I CHRNE ERBB2 GRIA2 HTR1B ITGAV NGFR | L-PROLINE; TOLBUTAMIDE; SARILUMAB |
| 8 | 143 | 0.0189 | 157.57 |
GOBP tube development GOCC cell surface GOBP striated muscle cell differentiation |
ESR2 CSNK1E NPC1 ROCK1 DNMT1 PDE4A PRKCE TESK1 DRD3 GRIN3A HDAC5 ITGA2B ACVR1 DPP9 EPHA2 FSHR GABRB2 ICAM1 ICAM3 LHCGR PDE6C ROCK2 SOD2 TNKS | HEROINd; L-ALANINE |
| 9 | 167 | 0.0187 | 201.30 | GOBP sex differentiation | SOD1 | CARBONIC ANHYDRASES; TRIHEXYPHENIDYLd; DEUTETRABENAZINE; MYRRH; PHENELZINE |
| 10 | 77 | 0.0124 | 93.58 | - | - | - |
aTop 3 biological gene sets, ranked by lowest nominal marginal p-value for each meta-locus.
bDrug-based gene sets selected based on DrugBank annotations and FDR < 0.05 significance levels for gene set analysis, as well as potential for nootropic function. Oncology drugs sets are excluded due to complex drug delivery procedures.
cTier 1 druggability annotations from Finan et al. (2017)38.
dDrug reported to be associated with cognitive impairment rather than nootropic function.