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
24687905
TITLE
Testing the role of circadian genes in conferring risk for psychiatric disorders.
ABSTRACT
Disturbed sleep and disrupted circadian rhythms are a common feature of psychiatric disorders, and many groups have postulated an association between genetic variants in circadian clock genes and psychiatric disorders. Using summary data from the association analyses of the Psychiatric Genomics Consortia (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we evaluated the evidence that common SNPs in genes encoding components of the molecular clock influence risk to psychiatric disorders. Initially, gene-based and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an expanded list of genes linked to control of circadian rhythms was analyzed. After correcting for multiple comparisons, none of the circadian genes were significantly associated with any of the three disorders. Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of P < 0.05, and none of the the variants identified in candidate studies of clock genes that were included in the PGC datasets were significant after correction for multiple testing. There was no evidence of an enrichment of associations in genes linked to control of circadian rhythms in human cells. Our results suggest that genes encoding components of the molecular clock are not good candidates for harboring common variants that increase risk to bipolar disorder, schizophrenia, or major depressive disorder.
2014 Wiley Periodicals, Inc.
DATE PUBLISHED
2014 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/02/05
accepted 2014/02/19
aheadofprint 2014/03/29
entrez 2014/04/02 06:00
pubmed 2014/04/02 06:00
medline 2014/12/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Byrne EM Byrne Enda M EM The University of Queensland, Queensland Brain Institute, Queensland, Australia.
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Pergadia ML Pergadia Michele L ML
Hickie IB Hickie Ian B IB
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Wray NR Wray Naomi R NR
INVESTIGATORS
JOURNAL
VOLUME: 165B
ISSUE: 3
TITLE: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISOABBREVIATION: Am. J. Med. Genet. B Neuropsychiatr. Genet.
YEAR: 2014
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1552-485X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Med Genet B Neuropsychiatr Genet
COUNTRY: United States
ISSNLINKING: 1552-4841
NLMUNIQUEID: 101235742
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
613608 Medical Research Council United Kingdom
DA019951 NIDA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
P60 AA011998 NIAAA NIH HHS United States
U01 MH085520 NIMH NIH HHS United States
U01 MH085520 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
circadian
clock
mood
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Bipolar Disorder genetics
CLOCK Proteins genetics
Circadian Clocks genetics
Depressive Disorder, Major genetics
Genetic Predisposition to Disease genetics
Humans genetics
Polymorphism, Single Nucleotide genetics
Schizophrenia genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.3.1.48 CLOCK Proteins
OTHER ID's
OTHERID SOURCE
NIHMS649107 NLM
PMC4397914 NLM