Table 2 Genes (nodes) belonging to the final networks that were already associated with OCD

ACC

CNVs [91]

NPY1R

Belongs to the G-protein-coupled receptor superfamily; Nervous system and immune system phenotype; Behavior/neurological phenotype; Mortality/aging.

NPY5R

Belongs to the G-protein-coupled receptor superfamily; Behavior/neurological phenotype.

GRIN1

Related to neurodevelopmental disorder; Relation with schizophrenia; Polymicrogyria.

RASGRF2

T-cell signaling response; Related to Alchoolism.

GWAs [45]

HLA-DPB1 ^††

Binds peptides derived from antigens that access the endocytic route of antigen presenting cells and presents them on the cell surface for recognition.

ADCY8 ^††

Catalyses the formation of cyclic AMP from ATP; Increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes; Related to mood disorder.

CNVs/

TGFBR1

Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest.

Exome [92]

UBE2Z

Encodes an enzyme which ubiquitinates proteins which participate in signaling pathways and apoptosis; Innate Immune System.

RABEP1

Vesicle-mediated transport.

OFC

CNVs

CDH10

Among its related pathways are ERK Signaling and Cell junction organization; GO annotations related to this gene include calcium ion binding; Mediate calcium-dependent cell-cell adhesion.

ASAH1

ASAH1 silencing increased basal and cAMP-dependent cortisol, establishing ASAH1 as a pivotal regulator of steroidogenic capacity in the human adrenal cortex.

ENTPD2

Among its related pathways are ATP/ITP metabolism and metabolism of nucleotides.

YES1

Encoded protein has tyrosine kinase activity and belongs to the src family of proteins.

IL17RD

Encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family, a component of the interleukin-17 receptor signaling complex.

TACR3

Belongs to a family of genes that function as receptors for tachykinins, characterized by interactions with G proteins.

VTI1B

SNARE protein.

GWAs

CHMP2B

Expressed in neurons of all major regions of the brain; Mutations in this gene result in one form of familial frontotemporal lobar degeneration.

PDE4D

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

PPP1R9B

Modulates excitatory synaptic transmission and dendritic spine morphology; Binds to actin filaments and shows cross-linking activity; Play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction; Plays a role in regulation of G-protein coupled receptor signaling; Related to schizophrenia.

SCARB2

Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.

Exome

COL4A1

Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects.

mRNA [93]

CACNB4

Encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Related to epilepsy.

NAC

CNVs

NAPB ^††

Associated with obsessive-compulsive personality disorder, amyotrophy, hereditary neuralgic and neurodegeneration with brain iron accumulation.

PDK4

Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.

SLC5A7 ^††

Transmembrane transporter that imports choline from the extracellular space into the neuron with high affinity.

SLC2A13

Transport related stereoisomers.

EPRS

Multifunctional protein that catalyzes the attachment of the cognate amino acid to the corresponding tRNA; Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy.

UBE2D1

Mediates the selective degradation of short-lived and abnormal proteins.

SCG5

Plays a role in regulating pituitary hormone secretion.

GWAs

KIT

Encodes a receptor tyrosine kinase; Related with multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types.

Exome

RAB25

Member of the RAS superfamily of small GTPases; Involved in membrane trafficking and cell survival; Cytoskeletal Signaling; Metabolism of proteins.

RHOD

Involved in endosome dynamics and reorganization of the actin cytoskeleton; Rho proteins interact with protein kinases and may serve as targets for activated GTPase.

RPL28

Encodes one of the small GTP-binding proteins in the Rho family shown to be associated with focal adhesions in endothelial cells.

RHOJ

Encodes one of the small GTP-binding proteins in the Rho family shown to be associated with focal adhesions in endothelial cells.

HERC5

Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells; Functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets.

PRKAA2

Catalytic subunit of the AMP-activated protein kinase (AMPK), a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits.

RAB13

Member of the Rab family of small G proteins; Plays a role in neuronal regeneration and regulation of neurite outgrowth.

mRNA

RPL35

Catalyze ribosomes, which consist of a small 40S subunit and a large 60S subunit and together are composed of 4 RNA species; rRNA processing in the nucleus and cytosol.

RPL6

Encodes a protein component of the 60S ribosomal subunit; rRNA processing in the nucleus and cytosol.

CN

CNVs

CSPG4

May also inhibit neurite outgrowth and growth cone collapse during axon regeneration.

GPSM2

Belongs to a family that modulate activation of G proteins; Required for cortical dynein-dynactin complex recruitment during metaphase.

PON3 ^††

Childhood aggressive behaviour measurement; Immune system phenotype.

LTBP1 ^††

Key regulator of TGFB1, TGFB2 and TGFB3 that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.

WWOX

Putative oxidoreductase; Acts as a tumor suppressor and plays a role in apoptosis; Multiple sclerosis.

ABCA2 ^††

May have a role in macrophage lipid metabolism and neural development.

CYFIP1 ^††

Regulates formation of membrane ruffles and lamellipodia; Plays a role in axon outgrowth.

CADM2 ^††

Important for synapse organization, providing regulated trans-synaptic adhesion; Preferentially binds to oligodendrocytes.

ELN

Encodes a protein of elastic fibers, which comprise part of the extracellular matrix and confer elasticity to organs and tissues.

MLXIPL

Encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily.

GWAs

SH3RF1

Has E3 ubiquitin-protein ligase activity; Innate Immune System.

HLA-DPA1 ^††

It plays a central role in the immune system by presenting peptides derived from extracellular proteins.

Exome

C4B

Encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway; Innate Immune System.

NR0B2

An unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain.

CALM1

Encodes calmodulin proteins, members of calcium-binding protein family. Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels.

NFE2

GO annotations related to this gene include DNA-binding transcription factor activity and transcription coactivator activity.

RNASE2

Is a non-secretory ribonuclease that belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily; Innate Immune System.

SERPINA1

Inhibitor of serine proteases; Innate Immune System; Related to mental retardation, x-linked, associated with fragile site fraxe.

FBLN1

Is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix; Cell adhesion; Degradation of the extracellular matrix.

DLG4

Is recruited into NMDA receptor and potassium channel clusters; Intellectual developmental disorder; Presynaptic function of Kainate receptors.

DLG2

Encodes a member of the membrane-associated guanylate kinase family; Protein-protein interactions at synapses; Tight junction; Related to autism disorder.

LYN

Encodes a tyrosine protein kinase; B cell receptor signaling pathway (KEGG); Immune response Fc epsilon RI pathway.

PT

CNVs

PRND

Mutations in this gene may lead to neurological disorders; Association with sporadic Creutzfeldt-Jakob disease; Immune system phenotype.

MUC4

May play a role in tumor progression.

GWAs

DTNBP1

Plays a role in synaptic vesicle trafficking and in neurotransmitter release; May play a role in actin cytoskeleton reorganization and neurite outgrowth; May modulate MAPK8 phosphorylation; Appears to promote neuronal transmission and viability, modulating PI3K signaling and influencing glutamatergic release; Modulates prefrontal cortical activity via the dopamine/D2 pathway.

Exome

JUND

Has been proposed to protect cells from p53-dependent senescence and apoptosis; MAPK signaling pathway.

AP1S1

Protein encoded by this gene is part of the clathrin coat assembly complex which links clathrin to receptors in coated vesicles, involved in endocytosis and Golgi processing.

JUN

Cognitive function measurement.

ACC/ OFC

CNVs

ADCYAP1 ^††

Related pathways are Signaling by GPCR and presynaptic function of Kainate receptors.

CACNA2D4

Encodes a protein in the voltage-dependent calcium channel complex; Related to bipolar disorder.

OFC/ CN

CNVs

PON1

Protein Coding gene; Diseases associated include microvascular complications of diabetes and amyotrophic lateral scclerosis.

Exome

C3

Plays a central role in the activation of complement system. Adaptive Immune System

OFC/ PT

Exome / mRNA

GBP4 ^††

Are induced by interferon and hydrolyze GTP to both GDP and GMP; Cytokine Signaling in Immune system.

NAC/ CN

Exome

RASD2

Belongs to the Ras superfamily of small GTPases and is enriched in the striatum. Encoded protein binds to mutant huntingtin (mHtt), mutated in Huntington disease (HD). Sumoylation of mHTT by this protein may cause degeneration of the striatum.

AKT1

Protein kinase family; AKT/PI3K forms a key component of many signalling pathways; Regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.

FAIM2

Protein Coding gene; Regulates Fas-mediated apoptosis in neurons by interfering with caspase-8 activation; Disease associated includes Ventilation Pneumonitis and OCD.

NAC/ CN/ PT

CNVs

CHRM5

Belong to a larger family of G protein-coupled receptors and influence many effects of acetylcholine in the central and peripheral nervous system; Important for prolonged dopamine release; Related to schizophrenia.