title: Polymorphisms in the homeobox gene OTX2 may be a risk factor for bipolar disorder.
abstract: We investigated the possible involvement of OTX2, a homeobox gene crucial for forebrain development, in the pathogenesis of schizophrenia and bipolar disorder. The disruption of this gene results in cortical malformations and causes serotonergic and dopaminergic cells in the midbrain to be expressed in aberrant locations. Resequencing of DNA from OTX2 exons and surrounding introns from 60 individuals (15 schizophrenia, 15 bipolar disorder, 15 depression, and 15 control) revealed two intronic polymorphisms, rs2277499 (C/T) and rs28757218 (G/T), but no other variations. The minor allele of rs2277499 (T) did not associate with clinical diagnosis. However, using a Taqman genotyping assay, we found the rs28757218 minor allele (T) in 30 out of 720 (4.2%) individuals with bipolar disorder but only in 6 out of 526 (1.1%) control individuals (odds ratio 3.5, 95% confidence interval 1.4-10.4, P = 0.003). On the other hand, the rs28757218 minor allele was only found in 6 out of 458 (1.3%) individuals with schizophrenia. All individuals with the rs28757218 polymorphism were heterozygous for the allele. Based on this positive case-control association finding, we conclude that variations in OTX2 might confer risk for the development of bipolar disorder.
authors.affiliation: Stanley Division of Developmental Neurovirology, Johns Hopkins University, Baltimore, Maryland 21287, USA. ssabunc1@jhmi.edu
authors.forename: Sarven
authors.initials: S
authors.lastname: Sabunciyan
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ragan
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
authors.forename: Faith
authors.initials: F
authors.lastname: Dickerson
authors.forename: Ida C
authors.initials: IC
authors.lastname: Llenos
authors.forename: Serge
authors.initials: S
authors.lastname: Weis
mesh_terms: D001741:Black or African American / Q000235:genetics; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D051857:Otx Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C497659:OTX2 protein, human; D051857:Otx Transcription Factors