PMID- 21647149
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20150708
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Linking)
VI  - 17
IP  - 7
DP  - 2012 Jul
TI  - A multi-tissue analysis identifies HLA complex group 9 gene methylation 
      differences in bipolar disorder.
PG  - 728-40
LID - 10.1038/mp.2011.64 [doi]
AB  - Epigenetic studies of DNA and histone modifications represent a new and important 
      activity in molecular investigations of human disease. Our previous 
      epigenome-wide scan identified numerous DNA methylation differences in 
      post-mortem brain samples from individuals affected with major psychosis. In this 
      article, we present the results of fine mapping DNA methylation differences at 
      the human leukocyte antigen (HLA) complex group 9 gene (HCG9) in bipolar disorder 
      (BPD). Sodium bisulfite conversion coupled with pyrosequencing was used to 
      interrogate 28 CpGs spanning  approximately 700 bp region of HCG9 in 1402 DNA samples from 
      post-mortem brains, peripheral blood cells and germline (sperm) of bipolar 
      disease patients and controls. The analysis of nearly 40 000 CpGs revealed 
      complex relationships between DNA methylation and age, medication as well as DNA 
      sequence variation (rs1128306). Two brain tissue cohorts exhibited lower DNA 
      methylation in bipolar disease patients compared with controls at an extended 
      HCG9 region (P=0.026). Logistic regression modeling of BPD as a function of 
      rs1128306 genotype, age and DNA methylation uncovered an independent effect of 
      DNA methylation in white blood cells (odds ratio (OR)=1.08, P=0.0077) and the 
      overall sample (OR=1.24, P=0.0011). Receiver operating characteristic curve A 
      prime statistics estimated a 69-72% probability of correct BPD prediction from a 
      case vs control pool. Finally, sperm DNA demonstrated a significant association 
      (P=0.018) with BPD at one of the regions demonstrating epigenetic changes in the 
      post-mortem brain and peripheral blood samples. The consistent multi-tissue 
      epigenetic differences at HCG9 argue for a causal association with BPD.
FAU - Kaminsky, Z
AU  - Kaminsky Z
AD  - The Krembil Family Epigenetics Laboratory, Neuroscience Department, Centre for 
      Addiction and Mental Health, Toronto, ON, Canada.
FAU - Tochigi, M
AU  - Tochigi M
FAU - Jia, P
AU  - Jia P
FAU - Pal, M
AU  - Pal M
FAU - Mill, J
AU  - Mill J
FAU - Kwan, A
AU  - Kwan A
FAU - Ioshikhes, I
AU  - Ioshikhes I
FAU - Vincent, J B
AU  - Vincent JB
FAU - Kennedy, J L
AU  - Kennedy JL
FAU - Strauss, J
AU  - Strauss J
FAU - Pai, S
AU  - Pai S
FAU - Wang, S-C
AU  - Wang SC
FAU - Petronis, A
AU  - Petronis A
LA  - eng
GR  - 186007/Canadian Institutes of Health Research/Canada
GR  - MH074127/MH/NIMH NIH HHS/United States
GR  - MH088413/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110607
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (HCG9 non-protein coding RNA, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Untranslated)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Bipolar Disorder/blood/*genetics/*metabolism
MH  - Brain/metabolism
MH  - Case-Control Studies
MH  - DNA Methylation/*genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Long Noncoding
MH  - RNA, Untranslated/genetics/*metabolism
MH  - Spermatozoa/metabolism
EDAT- 2011/06/08 06:00
MHDA- 2012/11/14 06:00
CRDT- 2011/06/08 06:00
PHST- 2011/06/08 06:00 [entrez]
PHST- 2011/06/08 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - mp201164 [pii]
AID - 10.1038/mp.2011.64 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2012 Jul;17(7):728-40. doi: 10.1038/mp.2011.64. Epub 2011 Jun 7.