A review and re-evaluation of an association between the NOTCH4 locus and schizophrenia

Zhenqi Wang, Jun Wei, Xuan Zhang, Yingjun Guo, Qi Xu, Shuzheng Liu, Jieping Shi, Yaqin Yu, Guizhi Ju, Yulin Li, Yan Shen

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


This work reviewed all the reports on the NOTCH4 gene in schizophrenia, which have been published since the gene was found to be associated with illness among a British population in 2000. The results from independent studies were inconsistent. Allelic heterogeneity, clinical diagnosis, ethnical backgrounds, and linkage disequilibrium (LD) structures in the human genome may be major reasons for poor replication. A couple of studies suggested that the NOTCH4 gene could play a role in a subgroup of the disease, such as early-onset schizophrenia and negative symptoms. A single study revealed a weak association of the NOTCH4 gene with frontal lobe brain volumes and a strong association with frontal lobe cognitive performance. A meta-analysis showed stronger evidence of the NOTCH4 association in family-based studies than in case-control studies. In a previous study, we found that rs520692, a single nucleotide polymorphism (SNP) at the NOTCH4 locus, was associated with schizophrenia in a Chinese population. In the present study, we applied a large sample size to re-evaluate our initial findings and then confirmed the rs520692 association with illness. The pairwise measures did not show strong LD between paired SNPs although the SNPs tested are located within a 34-kb region, suggesting that LD within the NOTCH4 gene has been broken rapidly by historical recombination in the Chinese population. Taken together, the NOTCH4 gene may be associated with schizophrenia but how the gene contributes to the etiology of the illness needs a further investigation.
Original languageEnglish
Pages (from-to)902-6
Number of pages5
JournalAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Issue number8
Publication statusPublished - 5 Dec 2006


  • Asian Continental Ancestry Group
  • Cognition
  • Female
  • Frontal Lobe
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins
  • Receptors, Notch
  • Schizophrenia


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