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Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins

Research output: Contribution to journalJournal article

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  • Araceli Rosa
  • Marco M. Picchioni
  • Sridevi Kalidindi
  • Caroline S. Loat
  • Joanne Knight
  • Timothea Toulopoulou
  • Ronald Vonk
  • Astrid C. van der Schot
  • Willem Nolen
  • René S. Kahn
  • Peter McGuffin
  • Robin M. Murray
  • Ian W. Craig
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<mark>Journal publication date</mark>5/06/2008
<mark>Journal</mark>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Issue number4
Volume147B
Number of pages4
Pages (from-to)459-462
Publication statusPublished
Early online date22/10/07
Original languageEnglish

Abstract

Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation. Some MZ female twin pairs are discordant for monogenic X linked disorders because of differential X inactivation. We postulated that similar mechanisms may also occur in disorders with more complex inheritance including BD and SZ. Examination of X-chromosome inactivation patterns in DNA samples from blood and/or buccal swabs in a series of 63 female MZ twin pairs concordant or discordant for BD or SZ and healthy MZ controls suggests a potential contribution from X-linked loci to discordance within twin pairs for BD but is inconclusive for SZ. Discordant female bipolar twins showed greater differences in the methylation of the maternal and paternal X alleles than concordant twin pairs and suggest that differential skewing of X-chromosome inactivation may contribute to the discordance observed for bipolar disorder in female MZ twin pairs and the potential involvement of X-linked loci in the disorder.