Schizophrenia genes and risk factors Enhanced links are provided by Diverse Kegg pathway analysis of GWAS and other networks

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Mental health information at Psych Central

 

In addition to the genes implicated in schizophrenia, a number of environmental risk factors have been implicated in the disease.These include effects during foetal development (famine and maternal infection during pregnancy) as well as during childhood and adulthood. These factors are compiled in this table. Starvation and viral infection activate the eif2alpha kinases eg EIF2AK2 gcn2 and leading to inhibition of the translation initiation factor eif2b, and the arrest of protein synthesis. EIF2B is paricularly important in the control of oligodendrocyte function, and activation of these pathways by some of the risk factors might be related to the oligodendrocyte cell death observed in schizophrenia. Further details Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health Toxoplasmosis Blog

Genes Kegg pathways for Schizophrenia genes

Multiple genes of small effect, whose risk promoting ability is conditioned by other genes and risk factors (Epistasis, gene/environment interactions). : For this reason any positive studies are reported.

  • See also:- The fox and the rabbits, environmental variables and population genetics.1: Replication problems in association studies and the untapped power of GWAS. ISRN Neurology, 2011
  • and:- Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes
  • eIF2B and oligodendrocyte survival: where nature and nurture meet in bipolar disorder and schizophrenia? Schiz Bull, 2007
  • Schizophrenia susceptibility genes converge on interlinked pathways related to glutamatergic transmission and long-term potentiation, oxidative stress and oligodendrocyte viability.Schiz Res, 2006
  • Toxoplasmosis and polygenic diseases: Extensive T.Gondii host/pathogen interactome enrichment in nine psychiatric or neurological disorders J.Pathogens, 2013

More info on most of these genes can be found here Recent genes will be linked from this page.

GWAS frome Genome.Gov ACSM1 ADM AGBL1 ANK3 ANXA1 ASTN2 ARHGAP4 ATP5SL BRP44 BTN2A2 BTN3A1 BTN3A2 ,BUCS1 C3orf39 C6orf10 C6orf105 CACNB2 CACNG5 CCDC60 CCDC68 CD48 CEACAM21 COL25A1 CNNM2 CNTN5 CNTNAP2 CSF2RA CTXN3 CYCSP44 DAOA DCAF6 ENPP4 ELAVL2 ERC2 FAM69A FAM110B FXR1 GABRR1 GPC1 GRIA2 HIST1H2AG, HIST1H2BJ HLA-DQA1 HLA-DRB3 IFLTD1 IFT88 IGSF22 IL3RA KCNJ3 LOC393076 LRRFIP1 LRRIQ3 LSM1 MECP2 MHC MIR137 MSRA MYO18B NALCN NAP5 NFKB1 . NKAPL NOTCH4 NPAS3 NRGN NRP1 PARD3 PLAA PTBP2 RIPK4 SLAMF1 . SLC12A2 SLC17A1 SLC17A3 SLCO6A1 PCGEM1 PGBD1 PHF8 POU3F2 PRSS16, POM121L2, PPARG PTPRU PTPRN2 RELN RIN2 RNF5 ROBO1 ROBO2 RYR2 SDCCAG8 TCF4 TMEM212 TNIK TRAF3 TRIM26 TSPAN18 VAV3 VIPR2 VRK2 ZKSCAN4 ZNF184 ZNF804A

 

Pre GWAS and single studies : See SZGene Allen et al, 2008 See also The Genetic Association database at NIH ... Genotator at Harvard University and HUGE navigator

ABCA1 ABCA13 ABCB1 ACE ACSL6 ACSM1 . ADA ADAM12 ADAMTS12 ADCYAP1 ADH1B ADIPOR2 ADORA1 ADRA1A ADSS AGA AGAP1 AGBL1 AHI AKT1 ALDH1A2 ALDH3B1 ALK ALOX12 AMACR ANK3 ANKAR ANKK1 ANXA7 APBA2 APC APOE APOL2 AR ARHGAP18 ARHGAP32 . ARHGEF10 . ARL17 ARRB1 . ARVCF ASAH1 ASNSD1 ASTN1 ASTN2 ATE1 ATF2 ATF6 ATG9 ATM ATN1 ATXN1 ATXN3 ATXN8OS AVP . B3GAT1 B3GAT2 BAK1 BCL9 BLOC1S3 BMP6 BRD1 BTN2A2 BTN3A1 BTN3A2 BZRP C6orf217 C10orf120 C11orf41 C18orf1 CAG CALR CAPZA2 CAV1 CBX2 CCDC102B CCDC60 CCKAR CDC27 CDC42, CDC42SE2 CDKN2A CEACAM21 CENTG2 CFB CHGA CHGB CHI3L1 CHN1 CHN2 CLDN5 CLINT1 CMYA5 CNP CNR1 CNR2 CPLX2 CPXM2 CREB3L1 CRH CRHR1 CSMD1 CSMD2 CSNK1E .CSPG5 CTNND2 CTXN3 CYP1A2 CYP2D6 CYP3A4 CYP3A5 DAAM1 DAAM2 DBH DCC DDR1 DDX31 DGCR2 DGCR5 DGCR6 . DGKH . DGKI DIRC1 DKK4 DLX1 DNMT3B DPYSL2 DNAJC9 DOCK4 DTNBP1 DUSP12 DYM DYNC2H1 EFNB2 EIF2S1 ELOVL2 ELP3 EML5 ENAH ENO2 ENTH ESD ESR1 EVPL FABP7 FAM71D FBP1 FBXL21 FBXL7 FBXO38 FLJ46361 FLNB FOLH1 FOXP2 FXR1 FXYD2 FXYD6 FYN FZD3 GALNT2 GALNT7 GC GDF8 GJA8 GLG1 GLT8D1 GLO1 GNAL GNAO1 GNAS GNB1L GNB3 GNL3 GNPAT GOPC GPC1 GPHN GPR78 GPR85 GTF2A1L GTF3C4 GULP1 HDAC3 HDAC4 HINT1 HIPK3 HIST1H2AG HIST1H2AH HIST1H2BJ HMBS HMX3 HP HRH2  HSPA1B HSPA1L HSPA12A HSPA1B HSPA1L HTF9C IMP5 IMPA2 IMPAD1 INTS6 IPO5 ITIH3 JARID2 KIAA1267 KIF2A KIF17 KLF5 KLF6 KLF13 KLH1AS KPNA3  KPNB3 KREMEN1 LAMA1 LARGE LG2 LGI1 LHPP LMX1A LMX1B LOC220433 LOC730216 LPL LRRC37A LOC387895 LRRC37A2 LRRTM1 MAD1L1 MAGI2 MAGI3 MAMDC1 MAN2A1, MAP4 MAP6 MAPK14 MAPK8IP2 MAPT MC5R MCHR1 MCHR2 MCP-2, MCTP2 MDGA1 ME2 MED12 MED15 MEGF10 MET MIM MIR132 MIR198 MIR206 MIR30E MLC1 MLL3 MMP3 MMP9 MOV10L1 MPP5 MPZL1 MRPL22 MT-haplo MTMR1A MTNR1B MTR MUTED MXRA5 NBPF10 NCAM1 NCAPD3 NCKAP5 NEK4 NEUROG1 NLGN2 NNMT NOS1 NOS1AP NPAS2 NPAS3 NPTN NPY NRGN NRN1 NSF NTNG1 NTNG2 NUMBL OLFML2B OGG1 OLIG2 OPCML OPRM1 SIGMAR1 ORMDL1 OSGEPL1 OXT PAFAH1B1 PADI2 PADI4 PAWR PAX6 PBRM1 PCK1 PCM1 PDCD1LG2 PDE4A PDE4D PDE7B PDLIM5 PDYN PEMT PFN4 PGAP1 PGBD1 PHOX2A PHOX2B PHTF2 PI4KA PIK3C2G PIK3C3 PIK4B PIP4K2A PIP5K2A PLA2G4 PLA2G4B PLA2G4C PLA2G6 PLAA PLAT PLCB1 PLEK2 PLP1 PLXNA2 PMS1 PNOC PNPLA8 PNPO POM121L2 POU3F2 PPAPDC1A PPARD PPP1R1B PPP3BB PPP3CB PPP3CC PRKAG2 PRKCA PRKCD PRKCH, PRODH PRSS16 PSAP PSEN2 PSKH1 PTBP2 PTGS2 PTK2 PTPN5 PTPN21 PTPRA PTPRM PTPRZ1 RANBP1 RAPGEF6 RASD2 RBP1 RCH2NH2 RELN RFX6 RGS2 RGS4 RGS5 .RHD RNLS RNR1 ROBO1 ROBO2 RPGRIP1L RPP21 RPRML RPS4XP16 RPS6KA5 RSRC1 RYR3 S100B SEMA3D SEMG2 SEPSECS SFRP1 SGCD SH3TC2 SHISA5 SIL1 SIRT5 SKP2 SLC12A2 SLC12A5 SLC12A9 SLC15A1 SLC17A1 SLC17A3 SLC22A23 SLC35F3 SLC39A8 SLC40A1 SLCO6A1 SLIT SLIT3 SMARCA2 SMARCC1 SOX10 SP4 SPARCL1 SPRY4 SREBF1 SREBF2 SRD5A2 ST8SIA2 SULT6B1 STH STON1 STON2 SULT4A1 ST8SIA2 TAAR6 TACC2 TAL1 TARBP1 TBP TBX1 TCERG1L TCF4 TCF7L2 TCP1 TF TGIF1 TGM2 TIMP3 TMC4 TMEM108 TNXB TP53 TP53I3 TRAF3IP1 TRIM71 TRMT2A TRPA1 TRPM1 TSKU TSPAN8 TUBA8 TXNDC5 U2AF UFD1L UHMK1 UPF3B USP46 vps34 VDR VRK2 WDFY2 WDR75 WNT3 WNT9B WWC1 XBP1 XRCC1 YWHAE YWHAH ZBED4 ZC3H18 ZDHHC8 ZMYND17 ZNF184 ZNF518A ZNF667 ZNF74 ZNF804A

To be mapped in KEGG pathways C1QB ADAMTSL3 FAS RAI1 DICER DGCR8 DCLK1 NRG3 GRN PPARA MAP2K7 TAS2R38 SV2A HLA-C*01:02 HLA-DRB1*03:01 HLA- B*08:01 ..LASP1 CRMP1 HHAT GRIN3A OXTR NRXN3 RUNDC2A ZEB1 ITGA8. IRS3P TPI1 CKB CACNB2 SDCCAG8 NTSR1 SLC23A3 CNPPD1 FAM134A c9orf5 CYP2E1 MYO5B HPS4 AS3MT CNNM2 NT5C2 AMBRA1 RELA CHRNA3 IGF2BP2 (Pathway GWAS RDH8 ACVR1, PSMD9 KCNAB1, KCNQ2, SLC17A3, ARCN1, COG7, STAB2, LRPAP1, STAB1, CXCL16, COL4A4 EXOSC3 CNR2 FAT1 SP8 CAMKK2 ITGB3 SLC30A3 PDZK1 TSNARE1 NDST3 ATXN2 ULK4 IL19 DLGAP2 MIR138-2 LSAMP PAK7 BRAP ITIH1 ITIH3 ITIH4 GPR88 NKCC1 GRIN3B GABRB3. DNMT3L SETD1A MBD2 FBXO45 IDO1 ENDOV LMAN2L CREB1

 

Sponaneous mutations in non familial schizophrenia: Exome sequencing Xu et al, 2011 ACOT6 ADAMTS3 ADCY7 CCDC108 CELF2 COL3A1 DGCR2 DPYD EDEM2 ESAM FAM3D FASTKD5 GIF GPR115 GPR153 INPP5A KLF12 LAMA2 MAGEC1 MTOR NPRL2 OR4C46 PAG1 PITPNM1 PLCL2 PML RB1CC1 RGS12 SAP30BP SLC26A7 SLC26A8 SPATA5 TEKT5 THBS1 TRAK1 TRRAP UGT1A4 VPS35 WDR11 ZNF530 (not all in the same individuals) LAMA2, DPYD, TRRAP and VPS39 Xu et al, 2012

Autozygosity (two chromosomal segments that are identical from a common ancestor are inherited from each parent: Relatively common in inbreeding) has been related to schizophrenia Keller et al, 2012
Risk factor (links to Wikipedia and Pubmed)

Prenatal

Childhood Adult Infections Association with other diseases

Dietary and environmental factors

  • Low Vitamin B12 levels: Vitamin B12 Deficiency can itself produce psychosis Kale at al, 2010 .Rajkumar and Jebaraj, 2008
  • A higher dietary intake of refined sugar and dairy products predicted a worse 2-year outcome of schizophrenia.Peet 2004
  • Adult women with a high intake of fish, omega-3 or omega-6 polyunsaturated fatty acids and vitamin D had a lower rate of psychosis Hedelin et al, 2010.
  • Favourable outcomes associated with a low percentage of total fat, and of fat from land animals and birds (composed mainly of saturated fat) High percentage of fat from vegetables, fish and seafood (having a relatively high content of unsaturated fatty acids) tended to be associated with a favourable course and outcome Christensen and Christensen, 1988
  • Levels of essential trace metals (Iron and Selenium) were reduced while levels of certain heavy metals (Lead, Chromium and Cadmium) were raised in schizophrenic patients Arinola et al, 2010.
  • Reduced hair concentrations of Zinc and Calcium and increases in the hair concentration of copper and cadmium have been reported in schizophrenic patients Rahman et al, 2009
  • Mercury related schizophreniforme psychosis Bader , 1952
  • Pesticides and disease database

Biochemistry, biomarkers and pathology

  • Lateral cerebral ventricle enlargement Weinberger et al, 1979
  • Cortical thinning in in prefrontal and temporal cortices Yang et al, 2010
  • Oligodendrocyte cell loss RSS feed
  • Decreased dentritic spine density in cortical regions RSS feed
  • Progressive gray matter loss Video
  • Decreased frontal cortex glutathione levels Gawryluk et al, 2011
  • Increased frontal cortex kynurenate levels (NMDA antagonist) Wonodi and Schwarcz, 2010.
  • N-acetyl cysteine, as a glutathione precursor, has been used with some success to treat schizophrenia Berk et al, 2008 RSS feed
  • A "P lymphocyte" is found in schizophrenics and their relatives, characterised by high cytoplasmic basophilia and leptochromatic nuclear structure.The cytoplasm often contains vacuoles and the nuclear shape is often irregular with one or more nucleoli visible Hirata-Hibi and Hayashi, 1993
  • High plasma homocysteine levels Haidemenos et al, 2007
  • Hippocampal inflammation as indexed by (11)C-(R)-PK11195 imaging Doorduin et al, 2009
  • miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652 as biomarkers in mononuclear leukocytes Lai et al, 2011
  • Elevated 3-hydroxykynurenine levels in plasma Condray et al, 2011
  • Activated kynurenine metabolism in fibroblasts from bipolar and schizophrenia patients. Cytokine challenge increases 3-hydroxykynurenine production Johansson et al, 2013
  • Schizophrenia patients frequently display reduced niacin flush responses Lien et al, 2013
  • A metabolomics plasma study identified higher concentration of ornithine and lower concentrations of arginine, glutamine, histidine and phosphatidylcholine ae C38:6 in schizophrenic patients He et al, 2012
  • Serum levels of IL1B, IL6 TNF and adiponectin increased in first episode schizophrenia Song et al, 2013
  • Decreased IL10 serum levels in first-episode drug-naïve schizophrenia (anti-inflammatory cytokine) Xiu et al, 2014
  • Pyroglutamic acid, sorbitol and tocopherol-a identified as peripheral blood mononuclear cells biomarkers Liu et al, 2014

Autoantibodies and antibodies in schizophrenia

Substance abuse , drugs and infections inducing psychosis and related symptoms and social

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