Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25108803
TITLE
DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.
METHODS NlmCategory: METHODS
We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies.
RESULTS NlmCategory: RESULTS
In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD.
CONCLUSIONS NlmCategory: CONCLUSIONS
Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.
Copyright 2015 Society of Biological Psychiatry. All rights reserved.
DATE PUBLISHED
2015 Feb 1
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/01/02
revised 2014/06/06
accepted 2014/06/08
aheadofprint 2014/07/01
entrez 2014/08/11 06:00
pubmed 2014/08/12 06:00
medline 2015/08/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Oh G Oh Gabriel G Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Wang SC Wang Sun-Chong SC Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan; Department of Public Health Sciences, Dalla Lana School of Public Health, Toronto, Ontario, Canada.
Pal M Pal Mrinal M Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Chen ZF Chen Zheng Fei ZF Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Khare T Khare Tarang T Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Tochigi M Tochigi Mamoru M Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan; Driskill Graduate Program in Life Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Ng C Ng Catherine C Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Yang YA Yang Yeqing A YA Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan; Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore Maryland.
Kwan A Kwan Andrew A Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Kaminsky ZA Kaminsky Zachary A ZA Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan; Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King׳s College, London, United Kingdom.
Mill J Mill Jonathan J Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan; Department of Psychology, University of Houston, Houston, Texas.
Gunasinghe C Gunasinghe Cerisse C Department of Psychology, University of Houston, Houston, Texas; University of Exeter Medical School, Exeter University, Exeter, United Kingdom.
Tackett JL Tackett Jennifer L JL Departments of Psychology and Psychiatry, University of Minnesota, Minneapolis, Minnesota.
Gottesman II Gottesman Irving I II Department of Biological Psychology, VU University Amsterdam, Netherlands Twin Register.
Willemsen G Willemsen Gonneke G and Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
de Geus EJ de Geus Eco J C EJ and Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
Vink JM Vink Jacqueline M JM and Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
Slagboom PE Slagboom P Eline PE Queensland Institute of Medical Research, Herston.
Wray NR Wray Naomi R NR The Queensland Brain Institute, University of Queensland, St Lucia, Australia; Department of Psychiatry, Washington University in St Louis, St Louis, Missouri.
Heath AC Heath Andrew C AC McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Montgomery GW Montgomery Grant W GW The Queensland Brain Institute, University of Queensland, St Lucia, Australia.
Turecki G Turecki Gustavo G Department of Psychiatry, McGill University, Montreal, Quebec, Canada; National Institute for Health Research Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service Foundation Trust, London.
Martin NG Martin Nicholas G NG The Queensland Brain Institute, University of Queensland, St Lucia, Australia.
Boomsma DI Boomsma Dorret I DI and Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
McGuffin P McGuffin Peter P Department of Psychology, University of Houston, Houston, Texas; University of Exeter Medical School, Exeter University, Exeter, United Kingdom.
Kustra R Kustra Rafal R Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Petronis A Petronis Art A Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan. Electronic address: art.petronis@camh.ca.
INVESTIGATORS
JOURNAL
VOLUME: 77
ISSUE: 3
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2015
MONTH: Feb
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
77689 Canadian Institutes of Health Research Canada
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
MH074127 NIMH NIH HHS United States
MH088413 NIMH NIH HHS United States
R01 MH074127 NIMH NIH HHS United States
R01 MH088413 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
DNA modification
Epigenetic outliers
Epigenetics
Heteroscedasticity
Major depressive disorder
Molecular networks
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
CpG Islands
Depressive Disorder, Major genetics
Epigenesis, Genetic genetics
Female genetics
Humans genetics
Leukocytes genetics
Male genetics
Microarray Analysis genetics
Middle Aged genetics
Prefrontal Cortex genetics
Spermatozoa genetics
Twins, Monozygotic genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS619819 NLM
PMC4277915 NLM