title: Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism.
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.
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: limchorhong@yahoo.com.
authors.forename: Chor Hong
authors.initials: CH
authors.lastname: Lim
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shamsul Mohd
authors.initials: SM
authors.lastname: Zain
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield S11WB, UK.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Reynolds
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohd Aizat
authors.initials: MA
authors.lastname: Zain
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Siti Norsyuhada
authors.initials: SN
authors.lastname: Roffeei
authors.affiliation: Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nor Zuraida
authors.initials: NZ
authors.lastname: Zainal
authors.affiliation: Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sharmilla
authors.initials: S
authors.lastname: Kanagasundram
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D017487:Ankyrins / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001714:Bipolar Disorder / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; C477344:LMAN2L protein, human; D037102:Lectins; D026901:Membrane Transport Proteins
keywords: ANK3; Bipolar disorder; LMAN2L; Polymorphism; Schizophrenia