Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism

Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3:54:157-62. doi: 10.1016/j.pnpbp.2014.05.017. Epub 2014 Jun 8.

Abstract

Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value=0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P=0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ, respectively) and GG (P=0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ.

Keywords: ANK3; Bipolar disorder; LMAN2L; Polymorphism; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ankyrins / genetics*
  • Asian People / genetics
  • Bipolar Disorder / ethnology
  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Lectins / genetics*
  • Male
  • Membrane Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*

Substances

  • ANK3 protein, human
  • Ankyrins
  • LMAN2L protein, human
  • Lectins
  • Membrane Transport Proteins