Journal of Neural Transmission

, Volume 125, Issue 1, pp 89–102 | Cite as

A systematic meta-analysis of the association of Neuregulin 1 (NRG1), d-amino acid oxidase (DAO), and DAO activator (DAOA)/G72 polymorphisms with schizophrenia

  • Vinita Jagannath
  • Miriam Gerstenberg
  • Christoph U. Correll
  • Susanne Walitza
  • Edna GrünblattEmail author
Psychiatry and Preclinical Psychiatric Studies - Original Article


The glutamate hypothesis of schizophrenia is related to the proposed dysregulation of d-amino acid oxidase (DAO), DAO activator (DAOA)/G72, and Neuregulin 1 (NRG1) genes. Genetic studies have shown significant associations between DAO, DAOA, NRG1 single-nucleotide polymorphisms (SNPs), and schizophrenia. The systematic literature search yielded 6, 5, and 18 new studies for DAO, DAOA, and NRG1 published after 2011 and not included in the previous SchizophreniaGene (SZGene) meta-analysis. We conducted meta-analyses of 20, 23, and 48 case–control studies, respectively, to comprehensively evaluate the association of 8 DAO, 12 DAOA, and 14 NRG1 SNPs with schizophrenia. The updated meta-analyses resulted in the following findings: the C-allele of DAO rs4623951 was associated with schizophrenia across all pooled studies [Odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.79–0.98, p = 0.02, N = 3143]; however, no new reports could be included. The G-allele of DAOA rs778293 was associated with schizophrenia in Asian patients (OR = 1.17, 95% CI = 1.08–1.27, p = 0.00008, N = 6117), and the T-allele of DAOA rs3916971 was associated with schizophrenia across all studies (OR = 0.84, 95% CI = 0.73–0.96, p = 0.01, N = 1765). Again, for both SNPs, no new eligible studies were available. After adding new reports, the T-allele of NRG1 SNP8NRG241930 (rs62510682) across all studies (OR = 0.95, 95% CI = 0.91–0.997, p = 0.04, N = 22,898) and in Caucasian samples (OR = 0.95, 95% CI = 0.90–0.99, p = 0.03, N = 16,014), and the C-allele of NRG1 rs10503929 across all studies (OR = 0.89, 95% CI = 0.81–0.97, p = 0.01, N = 6844) and in Caucasian samples (OR = 0.89, 95% CI = 0.81–0.98, p = 0.01, N = 6414) were protective against schizophrenia. Our systematic meta-analysis is the most updated one for the association of DAO, DAOA, and NRG1 SNPs with schizophrenia.


DAO/DAAO DAOA/G72 NRG1 SNP Meta-analysis Schizophrenia 


Compliance with ethical standards

Conflict of interest

Dr. Christoph U. Correll has been a consultant and/or advisor to or has received honoraria from: Alkermes, Allergan, Bristol-Myers Squibb, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medavante, Medscape, Neurocrine, Otsuka, Pfizer, ProPhase, Sunovion, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck and Pfizer. He received grant support from Takeda. Dr. Susanne Walitza has received lecture honoraria from Eli-Lilly, Astra Zeneca, Shire, and Opopharma in the last 5 years. Outside professional activities and interests are declared under the link of the University of Zurich The other authors declare no conflict of interest.


This project was supported by the Swiss Government Excellence Scholarship (2014.0826) to VJ.

Supplementary material

702_2017_1782_MOESM1_ESM.docx (5.5 mb)
Supplementary material 1 (DOCX 5629 kb)


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Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  1. 1.Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Centre for Child and Adolescent Psychiatry ResearchUniversity of ZurichSchlierenSwitzerland
  2. 2.The Zucker Hillside Hospital, Psychiatry Research, Northwell HealthGlen OaksUSA
  3. 3.Hofstra Northwell School of MedicineHempsteadUSA
  4. 4.The Feinstein Institute for Medical ResearchManhassetUSA
  5. 5.Neuroscience Center ZurichUniversity of Zurich and ETH ZurichZurichSwitzerland
  6. 6.Zurich Center for Integrative Human PhysiologyUniversity of ZurichZurichSwitzerland

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