title: Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins.
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.
authors.affiliation: Division of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Araceli
authors.initials: A
authors.lastname: Rosa
authors.forename: Marco M
authors.initials: MM
authors.lastname: Picchioni
authors.forename: Sridevi
authors.initials: S
authors.lastname: Kalidindi
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Loat
authors.forename: Joanne
authors.initials: J
authors.lastname: Knight
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.forename: Ronald
authors.initials: R
authors.lastname: Vonk
authors.forename: Astrid C
authors.initials: AC
authors.lastname: van der Schot
authors.forename: Willem
authors.initials: W
authors.lastname: Nolen
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: Ian W
authors.initials: IW
authors.lastname: Craig
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked; D006801:Humans; D010290:Parents; D012559:Schizophrenia / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*; D049951:X Chromosome Inactivation