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. Author manuscript; available in PMC: 2013 Mar 1.
Published in final edited form as: Biol Psychiatry. 2011 Dec 14;71(5):392–402. doi: 10.1016/j.biopsych.2011.09.034

Table 1.

Pathway analysis of 2,646 genes within exonic rare copy number variants (CNV) in Tourette syndrome (TS).

GeneGo (Metacore) Pathway Maps p-value Ratio RefSeq Genes # TS subjects
Proteolysis_Role of Parkin in the Ubiquitin-Proteasomal Pathway 9.6 × 10-5 6/24 CUL1, PSMD13, PARK2, SEPT5, SIAH1, TUBB4Q, TUBB8, UBE2J1 10
Neurophysiological process_GABA-A receptor life cycle 1.9 × 10-4 6/27 CLTB, GABRA1, GABRA6, GABRB1, GABRB2, GABRD, GABRG1, GABRG2, TUBB4Q, TUBB8 9
Cell adhesion_Histamine H1 receptor signaling in the interruption of cell barrier 5.8 × 10-4 7/45 CTNNA3, GNB4, GNG7, ITPR1, MYH11, MYLK3, OCLN, PPP1R12A, TLN1 17
Transport_Alpha-2 adrenergic receptor regulation of ion channels 7.7 × 10-4 7/47 CACNA1C, GNB4, GNG7, ITPR1, PRKACB, PRKCZ 11
Regulation of metabolism_Bile acids regulation of glucose and lipid metabolism via FXR 0.0012 6/37 ACACA, ACACB, APOC4, FOXO1, ADD1 5
Muscle contraction_ GPCRs in the regulation of smooth muscle tone 0.0015 9/83 ADRB2, CACNA1C, CAMK1, ITPR1, MYH11, MYLK3, OXT, OXTR, PPP1R12A, PRKACB 10
Cytoskeleton remodeling_Role of PKA in cytoskeleton reorganization 0.0018 6/40 ADD1, GNB4, GNG7, ITPR1, MYLK3, PPP1R12A, PRKACB 12
Regulation of lipid metabolism_Regulation of acetyl-CoA carboxylase 1 activity in lipogenic tissue 0.0019 4/17 ACACA, ACACB, PRKAB2, ADD1 4
Muscle contraction_S1P2 receptor-mediated smooth muscle contraction 0.0026 5/30 GNB4, GNG7, ITPR1, MYLK3, PPP1R12A, PRKCZ 10
Cell adhesion_Gap junctions 0.0026 5/30 GJA5, GJA8, OCLN, PRKCZ, TUBB4Q, TUBB8 8
PANTHER Pathways p-value Ratio RefSeq Genes # TS
Beta2 adrenergic receptor signaling 0.0047 8/44 PRKX, CACNA1C, GNB4, SNAP29, PRKACB, ADRB2, GNB1L, GNG7 12
Coenzyme A biosynthesis 0.0054 3/6 PANK2, PANK3, PANK4 3
5HT4 type receptor mediated signaling 0.010 6/31 HTT, HTR4, GNB4, SNAP29, GNB1L, GNG7 9
Muscarinic acetylcholine receptor 2 and 4 signaling 0.011 9/62 PRKX, SLC18A3, CACNA2D1, GNB4, SNAP29, PRKACB, CHAT, GNB1L, GNG7 12
Beta1 adrenergic receptor signaling 0.016 7/44 PRKX, CACNA1C, GNB4, SNAP29, PRKACB, GNB1L, GNG7 11
5HT1 type receptor mediated signaling 0.016 7/44 PRKX, HTT, GNB4, SNAP29, PRKACB, GNB1L, GNG7 11
Histamine H2 receptor mediated signaling 0.016 5/25 PRKX, GNB4, PRKACB, GNB1L, GNG7 10
Heterotrimeric G-protein signaling pathway-rod outer segment phototransduction 0.017 7/45 PRKX, GRK4, GRK6, GNB4, PRKACB, GNB1L, GNG7 13
Oxytocin receptor mediated signaling 0.026 8/60 PRKCZ, CACNA1C, OXTR, GNB4, SNAP29, PLCH2, GNB1L, GNG7 11
Muscarinic acetylcholine receptor 1 and 3 signaling pathway 0.028 8/61 ITPR1, PRKCZ, SLC18A3, GNB4, SNAP29, CHAT, GNB1L, GNG7 10
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway 0.036 16/166 PRKX, GRM7, ADRA18, CLTCL1, RGS14, GRK4, GRK6, HTR4, GNB4, CLTB, CKB, PRKACB, ADRB2, HTR7, GNB1L, GNG7 17
5HT2 type receptor mediated signaling 0.051 8/69 PRKCZ, CACNA1C, HTT, GNB4, SNAP29, PLCH2, GNB1L, GNG7 11
Histamine H1 receptor mediated signaling 0.058 6/47 ITPR1, PRKCA, GNB4, PLCH2, GNB1L, GNG7 10
IPA Pathways p-value Ratio RefSeq Genes # TS
Sphingolipid Metabolism 3.1 × 10-4 14/82 ARSB, ARSD, ARSE, ARSF, ARSH, ASAH2, GBA3, GLB1L2, GLB1L3, PPAP2A, SGMS1, SGPP1, SPHK1, SULF1 14
Glycosaminoglycan Degradation 0.0010 8/36 ARSB, FGFRL1, GBA3, GLB1L2, GLB1L3, HEXB, IDUA, SULF1 11
GABA Receptor Signaling 0.0060 8/47 AP1B1, GABRA1, GABRA6, GABRB1, GABRB2, GABRD, GABRG1, GABRG2 6
N-Glycan Degradation 0.027 5/29 EDEM1, GBA3, GLB1L2, GLB1L3, HEXB 5
Neuropathic Pain Signaling in Dorsal Horn Nucleus 0.033 11/102 CAMK1, GRIA1, GRINA, GRM7, ITPR1, PIK3C3, PLCH2, PRKACB, PRKCZ, TAC1, TACR1 14

The assessment of relative representation is compared to the entire genome, using the programs MetaCore (GeneGo, Inc), PANTHER, and Ingenuity Pathway Analysis (IPA). Ratios indicate the proportion of genes (PANTHER and IPA) or network objects (GeneGo Metacore) in known biological pathways that coincide with rare TS gene CNVs. The top five pathways with lowest p-values are shaded grey. Pathways with overlap between algorithms are highlighted in bold. “#TS” is number of unique TS subjects contributing at least one gene to the pathway result.