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Transcription profiling of human monozygotic twins discordant for bipolar disorder


ABSTRACT: To identify genes dysregulated in bipolar disorder (BD1) we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by ≥ 1.3-fold in 3 BD1 cases compared to their co-twins, and which were statistically (p ≤ 0.05) differentially expressed between the groups of BD1 cases and controls. Using qRT-PCR we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1, and PI4KCB, in at least 2 of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design1 our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis we identified up-regulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1. Experiment Overall Design: Three pairs of Monozygotic Twins which were discordant for Bipolar Disorder with psychotic features were examined. (n=6)

ORGANISM(S): Homo sapiens

SUBMITTER: Nicholas Matigian 

PROVIDER: E-GEOD-7036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway.

Matigian N N   Windus L L   Smith H H   Filippich C C   Pantelis C C   McGrath J J   Mowry B B   Hayward N N  

Molecular psychiatry 20070417 9


To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by >or=1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (P<or=0.05)  ...[more]

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