TY - JOUR
T1 - Polymorphisms in the homeobox gene OTX2 may be a risk factor for bipolar disorder
AU - Sabunciyan, Sarven
AU - Yolken, Robert
AU - Ragan, Christina M.
AU - Potash, James B.
AU - Nimgaonkar, Vishwajit L.
AU - Dickerson, Faith
AU - Llenos, Ida C.
AU - Weis, Serge
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2007/12/5
Y1 - 2007/12/5
N2 - 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.
AB - 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.
KW - Bipolar disorder
KW - Development
KW - Homeobox
KW - OTX2
KW - SNP
KW - Schizophrenia
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U2 - 10.1002/ajmg.b.30523
DO - 10.1002/ajmg.b.30523
M3 - Article
C2 - 17541950
AN - SCOPUS:36749022155
SN - 1552-4841
VL - 144
SP - 1083
EP - 1086
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 8
ER -