Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway.
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) differentially expressed between the groups of BD1 cases and controls. Using quantitative reverse transcriptase-polymerase chain reaction, we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design, our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we identified upregulation 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.
Matigian
N
N
Queensland Centre for Mental Health Research, Herston, QLD, Australia. Nick.Matigian@qimr.edu.au
Windus
L
L
Smith
H
H
Filippich
C
C
Pantelis
C
C
McGrath
J
J
Mowry
B
B
Hayward
N
N
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004200:Diseases in Twins / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D018433:Twin Studies as Topic; D014430:Twins, Monozygotic / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human