Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder across Diagnostic Boundaries

PLoS One. 2015 Sep 29;10(9):e0139413. doi: 10.1371/journal.pone.0139413. eCollection 2015.


Background: Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population.

Methods: A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models.

Results: Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing.

Discussion: We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Logistic Models
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics*
  • Sialyltransferases / genetics*
  • Young Adult


  • CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase
  • Sialyltransferases

Grant support

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120887). The work of T Park and IS H was supported by National Research Foundation (NRF) of Korea grant funded by the Korea government (MSIP) (No. 2012R1A3A2026438). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.