title: Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1.
abstract: BACKGROUND
  Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD).
  
  
  METHODS
  Here we describe a comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples.
  
  
  RESULTS
  Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for schizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling.
  
  
  CONCLUSIONS
  The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen-Woods
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Abdul
authors.initials: A
authors.lastname: Noor
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.forename: Georgina
authors.initials: G
authors.lastname: Hosang
authors.forename: Sagar V
authors.initials: SV
authors.lastname: Parikh
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Julia
authors.initials: J
authors.lastname: Forte
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Hu
authors.forename: Hugh M D
authors.initials: HM
authors.lastname: Gurling
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.forename: John
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), R-32, 250 College Street, Toronto, ON M5T 1R8, Canada. john.vincent@camh.ca.
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002170:Canada; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D015203:Reproducibility of Results; D025521:Tumor Suppressor Proteins; D006113:United Kingdom; D055815:Young Adult
chemical_list: C477880:CSMD1 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human; D025521:Tumor Suppressor Proteins