Skip to main content
SpringerLink
Log in

Transmission disequilibrium test provides evidence of association between promoter polymorphisms in 22q11 gene DGCR14 and schizophrenia

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Recent research has suggested that the DiGeorge syndrome critical region gene 14 (DGCR14) exhibits activity differences of more than 1.5 fold between the haplotypes of the variants in the promoter region. DGCR14 is located at 22q11.21, an acknowledged region for susceptibility to schizophrenia. To test the hypothesis that DGCR14 may be involved in the etiology of the disease, we carried out a family-based association study between the reported functional markers and schizophrenia in 235 Chinese Han trios. We found significant evidence of preferential transmission of the promoter variants of DGCR14 across all the trios (Best p-value = 0.00038, Global p-value = 0.0008). The positive results have suggested that DGCR14 is likely to play an important role in the etiology of schizophrenia in the Chinese Han population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • A Aleman RS Kahn JP Selten (2003) ArticleTitleSex differences in the risk of schizophrenia: evidence from meta-analysis Arch Gen Psychiatry 60 565–571 Occurrence Handle12796219 Occurrence Handle10.1001/archpsyc.60.6.565

    Article  PubMed  Google Scholar 

  • R Bell J Munro C Russ JF Powell A Bruinvels RW Kerwin DA Collier (2000) ArticleTitleSystematic screening of the 14-3-3 eta (eta) chain gene for polymorphic variants and case-control analysis in schizophrenia Am J Med Genet 96 736–743 Occurrence Handle11121172 Occurrence Handle1:STN:280:DC%2BD3M%2FmsVKksw%3D%3D Occurrence Handle10.1002/1096-8628(20001204)96:6<736::AID-AJMG8>3.0.CO;2-2

    Article  PubMed  CAS  Google Scholar 

  • HY Chen JI Yeh CJ Hong CH Chen (2005) ArticleTitleMutation analysis of ARVCF gene on chromosome 22q11 as a candidate for a schizophrenia gene Schizophr Res 72 275–277 Occurrence Handle15560973 Occurrence Handle10.1016/j.schres.2004.03.004

    Article  PubMed  Google Scholar 

  • W Chen S Duan J Zhou Y Sun Y Zheng N Gu G Feng L He (2004) ArticleTitleA case-control study provides evidence of association for a functional polymorphism -197C/G in XBP1 to schizophrenia and suggests a sex-dependent effect Biochem Biophys Res Commun 319 866–870 Occurrence Handle15184063 Occurrence Handle1:CAS:528:DC%2BD2cXkslWms78%3D Occurrence Handle10.1016/j.bbrc.2004.05.060

    Article  PubMed  CAS  Google Scholar 

  • WY Chen YY Shi YL Zheng XZ Zhao GJ Zhang SQ Chen PD Yang L He (2004) ArticleTitleCase-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8 Hum Mol Genet 13 2991–2995 Occurrence Handle15489219 Occurrence Handle1:CAS:528:DC%2BD2cXhtVSkt7fI Occurrence Handle10.1093/hmg/ddh322

    Article  PubMed  CAS  Google Scholar 

  • A De Luca E Conti N Grifone F Amati G Spalletta C Caltagirone G Bonaviri A Pasini M Gennarelli B Stefano L Berti G Mittler M Meisterernst B Dallapiccola G Novelli (2003) ArticleTitleAssociation study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia Am J Med Genet B Neuropsychiatr Genet 116 IssueID1 32–35 Occurrence Handle12497610 Occurrence Handle10.1002/ajmg.b.10008

    Article  PubMed  Google Scholar 

  • A De Luca A Pasini F Amati A Botta G Spalletta S Alimenti F Caccamo E Conti J Trakalo F Macciardi B Dallapiccola G Novelli (2001) ArticleTitleAssociation study of a promoter polymorphism of UFD1L gene with schizophrenia Am J Med Genet 105 IssueID6 529–533 Occurrence Handle11496370 Occurrence Handle1:STN:280:DC%2BD3MvltVWjtw%3D%3D Occurrence Handle10.1002/ajmg.1489

    Article  PubMed  CAS  Google Scholar 

  • JM Devaney EA Donarum KM Brown J Meyer G Stober KP Lesch et al. (2002) ArticleTitleNo missense mutation of WKL1 in a subgroup of probands with schizophrenia Mol Psychiatry 7 419–423 Occurrence Handle11986987 Occurrence Handle1:CAS:528:DC%2BD38Xjs1Kis78%3D Occurrence Handle10.1038/sj.mp.4001022

    Article  PubMed  CAS  Google Scholar 

  • S Duan R Gao Q Xing J Du Z Liu Q Chen H Wang G Feng L He (2005) ArticleTitleA family-based association study of schizophrenia with polymorphisms at three candidate genes Neurosci Lett 379 IssueID1 32–36 Occurrence Handle15814194 Occurrence Handle1:CAS:528:DC%2BD2MXivF2jsbY%3D Occurrence Handle10.1016/j.neulet.2004.12.040

    Article  PubMed  CAS  Google Scholar 

  • F Dudbridge (2003) ArticleTitlePedigree disequilibrium tests for multilocus haplotypes Genet Epidemiol 25 115–121 Occurrence Handle12916020 Occurrence Handle10.1002/gepi.10252

    Article  PubMed  Google Scholar 

  • JB Fan WY Chen JX Tang S Li NF Gu GY Feng G Breen D St Clair L He (2002) ArticleTitleFamily-based association studies of COMT gene polymorphisms and schizophrenia in the Chinese population Mol Psychiatry 7 446–447 Occurrence Handle12082558 Occurrence Handle1:CAS:528:DC%2BD38XkslKmtrw%3D Occurrence Handle10.1038/sj.mp.4001001

    Article  PubMed  CAS  Google Scholar 

  • JB Fan J Ma CS Zhang JX Tang NF Gu GY Feng D St Clair L He (2003) ArticleTitleA family-based association study of T1945C polymorphism in the proline dehydrogenase gene and schizophrenia in the Chinese population Neurosci Lett 338 252–254 Occurrence Handle12581843 Occurrence Handle1:CAS:528:DC%2BD3sXhtVant7g%3D Occurrence Handle10.1016/S0304-3940(02)01362-9

    Article  PubMed  CAS  Google Scholar 

  • JB Fan CS Zhang NF Gu XW Li WW Sun HY Wang GY Feng D St Clair L He (2005) ArticleTitleCatechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis Biol Psychiatry 57 139–144 Occurrence Handle15652872 Occurrence Handle1:CAS:528:DC%2BD2MXkvFajtA%3D%3D Occurrence Handle10.1016/j.biopsych.2004.10.018

    Article  PubMed  CAS  Google Scholar 

  • M Flaum X Amador J Gorman HS Bracha W Edell T McGlashan A Pandurangi KS Kendler D Robinson J Lieberman A Ontiveros M Tohen P McGorry G Tyrrell S Arndt NC Andreasen (1997) DSM-IV field trial for schizophrenia and other psychotic disorders. DSM-IV Sourcebook, vol 4 American Psychiatric Association Washington, DC 687–713

    Google Scholar 

  • T Hashimoto DW Volk SM Eggan K Mirnics JN Pierri Z Sun AR Sampson DA Lewis (2003) ArticleTitleGene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia J Neurosci 23 IssueID15 6315–6326 Occurrence Handle12867516 Occurrence Handle1:CAS:528:DC%2BD3sXlvVCgs7c%3D

    PubMed  CAS  Google Scholar 

  • T Hayakawa H Ishiguro M Toru H Hamaguchi T Arinami (1998) ArticleTitleSystematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in schizophrenics Psychiatr Genet 8 33–36 Occurrence Handle9564686 Occurrence Handle1:STN:280:DyaK1c3isFyktg%3D%3D

    PubMed  CAS  Google Scholar 

  • B Hoogendoorn SL Coleman CA Guy SK Smith MC O’Donovan PR Buckland (2004) ArticleTitleFunctional analysis of polymorphisms in the promoter regions of genes on 22q11 Hum Mutat 24 IssueID1 35–42 Occurrence Handle15221787 Occurrence Handle1:CAS:528:DC%2BD2cXmtlShsbo%3D Occurrence Handle10.1002/humu.20061

    Article  PubMed  CAS  Google Scholar 

  • A Jablensky N Sartorius G Ernberg M Anker A Korten JE Cooper R Day A Bertelsen (1992) ArticleTitleSchizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study Psychol Med Monogr [Suppl] 20 1–97 Occurrence Handle1:STN:280:DyaK383ivVyquw%3D%3D Occurrence Handle10.1017/S0264180100000904

    Article  CAS  Google Scholar 

  • M Karayiorgou JA Gogos (2004) ArticleTitleThe molecular genetics of the 22q11-associated schizophrenia Brain Res Mol Brain Res 132 IssueID2 95–104 Occurrence Handle15582150 Occurrence Handle1:CAS:528:DC%2BD2cXhtVCktLvF Occurrence Handle10.1016/j.molbrainres.2004.09.029

    Article  PubMed  CAS  Google Scholar 

  • A Kurumaji H Nomoto T Yoshikawa Y Okubo M Toru (2000) ArticleTitleAn association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample J Neural Transm 107 IssueID4 491–500 Occurrence Handle11215759 Occurrence Handle1:CAS:528:DC%2BD3cXjslSqtrw%3D Occurrence Handle10.1007/s007020070090

    Article  PubMed  CAS  Google Scholar 

  • N Laird S Horvath X Xu (2000) ArticleTitleImplementing a unified approach to family based tests of association Genet Epi 19 IssueID[Suppl 1] S36–S42 Occurrence Handle10.1002/1098-2272(2000)19:1+<::AID-GEPI6>3.0.CO;2-M

    Article  Google Scholar 

  • CM Lewis DF Levinson LH Wise LE DeLisi RE Straub I Hovatta NM Williams SG Schwab AE Pulver SV Faraone LM Brzustowicz CA Kaufmann DL Garver HM Gurling E Lindholm H Coon HW Moises W Byerley SH Shaw A Mesen R Sherrington FA O’Neill D Walsh KS Kendler J Ekelund T Paunio J Lonnqvist L Peltonen MC O’Donovan MJ Owen DB Wildenauer W Maier G Nestadt JL Blouin SE Antonarakis BJ Mowry JM Silverman RR Crowe CR Cloninger MT Tsuang D Malaspina JM Harkavy-Friedman DM Svrakic AS Bassett J Holcomb G Kalsi A McQuillin J Brynjolfson T Sigmundsson H Petursson E Jazin T Zoega T Helgason (2003) ArticleTitleGenome scan meta-analysis of schizophrenia and bipolar disorder, part II. Schizophrenia Am J Hum Genet 73 IssueID1 34–48 Occurrence Handle12802786 Occurrence Handle1:CAS:528:DC%2BD3sXlsVOitL8%3D Occurrence Handle10.1086/376549

    Article  PubMed  CAS  Google Scholar 

  • DA Lewis T Hashimoto DW Volk (2005) ArticleTitleCortical inhibitory neurons and chizophrenia Nat Rev Neurosci 6 IssueID4 312–324 Occurrence Handle15803162 Occurrence Handle1:CAS:528:DC%2BD2MXivVarsbc%3D Occurrence Handle10.1038/nrn1648

    Article  PubMed  CAS  Google Scholar 

  • EA Lindsay EL Harvey PJ Scambler A Baldini (1998) ArticleTitleES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like gene Hum Mol Genet 7 IssueID4 629–635 Occurrence Handle9499415 Occurrence Handle1:CAS:528:DyaK1cXisVemurY%3D Occurrence Handle10.1093/hmg/7.4.629

    Article  PubMed  CAS  Google Scholar 

  • TM Maynard GT Haskell AZ Peters L Sikich JA Lieberman AS LaMantia (2003) ArticleTitleA comprehensive analysis of 22q11 gene expression in the developing and adult brain Proc Natl Acad Sci USA 100 IssueID24 14433–14438 Occurrence Handle14614146 Occurrence Handle1:CAS:528:DC%2BD3sXpsFGhs7Y%3D Occurrence Handle10.1073/pnas.2235651100

    Article  PubMed  CAS  Google Scholar 

  • KA McGhee DW Morris S Schwaiger JM Nangle G Donohoe S Clarke D Meagher J Quinn P Scully JL Waddington M Gill A Corvin (2005) ArticleTitleInvestigation of the apolipoprotein-L (APOL) gene family and schizophrenia using a novel DNA pooling strategy for public database SNPs Schizophr Res 76 IssueID2–3 231–238 Occurrence Handle15949655 Occurrence Handle10.1016/j.schres.2005.01.006

    Article  PubMed  Google Scholar 

  • J Meyer A Huberth G Ortega YV Syagailo S Jatzke R Mossner TM Strom I Ulzheimer-Teuber G Stober A Schmitt KP Lesch (2001) ArticleTitleA missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree Mol Psychiatry 6 IssueID3 302–306 Occurrence Handle11326298 Occurrence Handle1:CAS:528:DC%2BD3MXisFyls7w%3D Occurrence Handle10.1038/sj.mp.4000869

    Article  PubMed  CAS  Google Scholar 

  • ML Mimmack M Ryan H Baba J Navarro-Ruiz S Iritani RL Faull PJ McKenna PB Jones H Arai M Starkey PC Emson S Bahn (2002) ArticleTitleGene expression analysis in SZ: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for SZ on chromosome 22 Proc Natl Acad Sci USA 99 4680–4685 Occurrence Handle11930015 Occurrence Handle1:CAS:528:DC%2BD38XivFSgsrY%3D Occurrence Handle10.1073/pnas.032069099

    Article  PubMed  CAS  Google Scholar 

  • J Mukai H Liu RA Burt DE Swor WS Lai M Karayiorgou JA Gogos (2004) ArticleTitleEvidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia Nat Genet 36 725–731 Occurrence Handle15184899 Occurrence Handle1:CAS:528:DC%2BD2cXlt1Cku74%3D Occurrence Handle10.1038/ng1375

    Article  PubMed  CAS  Google Scholar 

  • KC Murphy (2002) ArticleTitleSchizophrenia and velo-cardio-facial syndrome Lancet 359 426–430 Occurrence Handle11844533 Occurrence Handle10.1016/S0140-6736(02)07604-3

    Article  PubMed  Google Scholar 

  • S Purcell SS Cherny PC Sham (2003) ArticleTitleGenetic Power Calculator: design of linkage and association genetic mapping studies of complex traits Bioinformatics 19 149–150 Occurrence Handle12499305 Occurrence Handle1:CAS:528:DC%2BD3sXltF2ksQ%3D%3D Occurrence Handle10.1093/bioinformatics/19.1.149

    Article  PubMed  CAS  Google Scholar 

  • GP Reynolds Z Abdul-Monim JC Neill ZJ Zhang (2004) ArticleTitleCalcium binding protein markers of GABA deficits in schizophrenia–postmortem studies and animal models Neurotox Res 6 IssueID1 57–61 Occurrence Handle15184106 Occurrence Handle10.1007/BF03033297

    Article  PubMed  Google Scholar 

  • P Rizzu EA Lindsay C Taylor H O’Donnell A Levy P Scambler A Baldini (1996) ArticleTitleCloning and comparative mapping of a gene from the commonly deleted region of DiGeorge and Velocardiofacial syndromes conserved in C. elegans Mamm Genome 7 IssueID9 639–643 Occurrence Handle8703114 Occurrence Handle1:CAS:528:DyaK28XmvFOjur0%3D Occurrence Handle10.1007/s003359900197

    Article  PubMed  CAS  Google Scholar 

  • S Saito M Ikeda N Iwata T Suzuki T Kitajima Y Yamanouchi Y Kinoshita N Takahashi T Inada N Ozaki (2005) ArticleTitleNo association was found between a functional SNP in ZDHHC8 and schizophrenia in a Japanese case-control population Neurosci Lett 374 21–24 Occurrence Handle15631889 Occurrence Handle1:CAS:528:DC%2BD2MXnvF2r Occurrence Handle10.1016/j.neulet.2004.10.015

    Article  PubMed  CAS  Google Scholar 

  • T Saito F Guan DF Papolos N Rajouria CS Fann HM Lachman (2001) ArticleTitlePolymorphism in SNAP29 gene promoter region associated with schizophrenia Mol Psychiatry 6 IssueID2 193–201 Occurrence Handle11317222 Occurrence Handle1:CAS:528:DC%2BD3MXhsFGlurc%3D Occurrence Handle10.1038/sj.mp.4000825

    Article  PubMed  CAS  Google Scholar 

  • AR Sanders I Rusu J Duan JE Vander Molen C Hou SG Schwab DB Wildenauer M Martinez PV Gejman (2005) ArticleTitleHaplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia Mol Psychiatry 10 353–365 Occurrence Handle15340358 Occurrence Handle1:CAS:528:DC%2BD2MXislahsL4%3D Occurrence Handle10.1038/sj.mp.4001586

    Article  PubMed  CAS  Google Scholar 

  • L Sinibaldi A De Luca E Bellacchio E Conti A Pasini C Paloscia G Spalletta C Caltagirone A Pizzuti B Dallapiccola (2004) ArticleTitleMutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia Hum Mutat 24 IssueID6 534–535 Occurrence Handle15532024 Occurrence Handle10.1002/humu.9292 Occurrence Handle1:CAS:528:DC%2BD2MXhs1OmsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • ZY Sun J Wei L Xie Y Shen SZ Liu GZ Ju JP Shi YQ Yu X Zhang Q Xu GP Hemmings (2004) ArticleTitleThe CLDN5 locus may be involved in the vulnerability to schizophrenia Eur Psychiatry 19 IssueID6 354–357 Occurrence Handle15363474 Occurrence Handle10.1016/j.eurpsy.2004.06.007

    Article  PubMed  Google Scholar 

  • K Takase T Ohtsuki O Migita M Toru T Inada K Yamakawa-Kobayashi T Arinami (2001) ArticleTitleAssociation of ZNF74 gene genotypes with age-at-onset of schizophrenia Schizophr Res 52 IssueID3 161–165 Occurrence Handle11705709 Occurrence Handle1:STN:280:DC%2BD3MnltlClsA%3D%3D Occurrence Handle10.1016/S0920-9964(00)00191-2

    Article  PubMed  CAS  Google Scholar 

  • K Toyooka T Muratake T Tanaka S Igarashi H Watanabe H Takeuchi S Hayashi M Maeda M Takahashi S Tsuji T Kumanishi Y Takahashi (1999) ArticleTitle14-3-3 protein eta chain gene (YWHAH) polymorphism and its genetic association with schizophrenia Am J Med Genet 88 164–167 Occurrence Handle10206237 Occurrence Handle1:STN:280:DyaK1M3itFSkug%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(19990416)88:2<164::AID-AJMG13>3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

  • R Verma M Mukerji D Grover C B-Rao SK Das S Kubendran S Jain SK Brahmachari (2005) ArticleTitleMLC1 gene is associated with schizophrenia and bipolar disorder in Southern India Biol Psychiatry 58 IssueID1 16–22 Occurrence Handle15992519 Occurrence Handle1:CAS:528:DC%2BD2MXlslyntbk%3D Occurrence Handle10.1016/j.biopsych.2005.03.027

    Article  PubMed  CAS  Google Scholar 

  • NM Williams MJ Owen (2004) ArticleTitleGenetic abnormalities of chromosome 22 and the development of psychosis Curr Psychiatr Rep 6 IssueID3 176–182

    Google Scholar 

  • AH Wong F Macciardi T Klempan W Kawczynski CL Barr S Lakatoo Mg Won C Buckle J Trakalo E Boffa J Oak MH Azevedo A Dourado I Coelho A Macedo A Vicente J Valente CP Ferreira MT Pato CN Pato JL Kennedy HH Van Tol (2003) ArticleTitleIdentification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3eta gene Mol Psychiatry 8 156–166 Occurrence Handle12610648 Occurrence Handle1:CAS:528:DC%2BD3sXhsFWrsrw%3D Occurrence Handle10.1038/sj.mp.4001237

    Article  PubMed  CAS  Google Scholar 

  • L Ye Z Sun L Xie S Liu G Ju J Shi Y Yu X Zhang J Wei Q Xu Y Shen (2005) ArticleTitleFurther study of a genetic association between the CLDN5 locus and schizophrenia Schizophr Res 75 139–141 Occurrence Handle15820333 Occurrence Handle10.1016/j.schres.2004.11.003

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bio-X Center, Shanghai Jiao Tong University, Shanghai, China

    H. Wang, S. Duan, J. Du, X. Li, Z. Zhang & Y. Wang

  2. Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    H. Wang, S. Duan, J. Du, X. Li & L. He

  3. Life Science School, Ningxia University, Yinchuan, China

    H. Wang & Y. Wang

  4. Shanghai Jiao Tong University Medical School, Shanghai, China

    Y. Xu & G. Huang

  5. Shanghai Institute of Mental Health, Shanghai, China

    G. Feng

  6. NHGG, Bio-X Center, Shanghai Jiao Tong University, Shanghai, China

    L. He

Authors
  1. H. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L. He
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

The first and second authors have contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, H., Duan, S., Du, J. et al. Transmission disequilibrium test provides evidence of association between promoter polymorphisms in 22q11 gene DGCR14 and schizophrenia. J Neural Transm 113, 1551–1561 (2006). https://doi.org/10.1007/s00702-005-0420-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0420-3

Search

Navigation