Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins
AU - Rosa, Araceli
AU - Picchioni, Marco M.
AU - Kalidindi, Sridevi
AU - Loat, Caroline S.
AU - Knight, Joanne
AU - Toulopoulou, Timothea
AU - Vonk, Ronald
AU - van der Schot, Astrid C.
AU - Nolen, Willem
AU - Kahn, René S.
AU - McGuffin, Peter
AU - Murray, Robin M.
AU - Craig, Ian W.
N1 - (c) 2007 Wiley-Liss, Inc.
PY - 2008/6/5
Y1 - 2008/6/5
N2 - 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.
AB - 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.
KW - Bipolar Disorder
KW - Chromosomes, Human, X
KW - DNA Methylation
KW - Diseases in Twins
KW - Female
KW - Genetic Diseases, X-Linked
KW - Humans
KW - Parents
KW - Schizophrenia
KW - Twins, Monozygotic
KW - X Chromosome Inactivation
U2 - 10.1002/ajmg.b.30616
DO - 10.1002/ajmg.b.30616
M3 - Journal article
C2 - 17955481
VL - 147B
SP - 459
EP - 462
JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 4
ER -