Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
17339520
TITLE
Anxiety and comorbid measures associated with PLXNA2.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
Reduction in adult neurogenesis has been proposed as a mechanism for onset of depression. Semaphorins and their coreceptors, plexins, have been implicated in nervous system development and in adult neurogenesis. A recent genomewide association study of schizophrenia identified a variant of the gene encoding plexin A2 (PLXNA2) to be most consistently associated across study samples. Common genetic liabilities have been reported between psychiatric and psychological measures, but few examples exist of common genetic variants.
OBJECTIVE NlmCategory: OBJECTIVE
To perform a genetic association study between 6 single nucleotide polymorphisms from the PLXNA2 gene (rs3736963, rs2767565, rs752016, rs1327175, rs2478813, and rs716461) and anxiety, depression, neuroticism, and psychological distress.
DESIGN NlmCategory: METHODS
Extreme discordant and concordant siblings.
SETTING NlmCategory: METHODS
Australia.
PARTICIPANTS NlmCategory: METHODS
Study participants were selected with respect to extreme neuroticism scores from a population cohort of 18 742 twin individuals and their siblings. The participants and their parents (if blood or buccal samples were available) were genotyped, for a total of 2854 genotyped individuals from 990 families. Of these, 624 individuals with a diagnosis of anxiety or depression from 443 families were used in the association analysis.
MAIN OUTCOME MEASURES NlmCategory: METHODS
All the participants completed the Composite International Diagnostic Interview, the 23-item Neuroticism scale of the revised Eysenck Personality Questionnaire, and the 10-item Kessler Psychological Distress Scale. Diagnoses of DSM-IV depression and anxiety were determined from the Composite International Diagnostic Interview.
RESULTS NlmCategory: RESULTS
There was evidence of an allelic association between rs2478813 (and other single nucleotide polymorphisms correlated with it) and anxiety, depression, neuroticism, and psychological distress; the association with anxiety is significant after Bonferroni correction for multiple testing (empirical P<.001). The mouse ortholog of PLXNA2 is located in a highly significant linkage region previously reported for anxiety in mice.
CONCLUSION NlmCategory: CONCLUSIONS
PLXNA2 is a candidate for causal variation in anxiety and in other psychiatric disorders through its comorbidity with anxiety.
DATE PUBLISHED
2007 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2007/03/07 09:00
medline 2007/06/09 09:00
entrez 2007/03/07 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wray NR Wray Naomi R NR Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, QLD 4029, Australia. naomi.wray@qimr.edu.au
James MR James Michael R MR
Mah SP Mah Steven P SP
Nelson M Nelson Matthew M
Andrews G Andrews Gavin G
Sullivan PF Sullivan Patrick F PF
Montgomery GW Montgomery Grant W GW
Birley AJ Birley Andrew J AJ
Braun A Braun Andreas A
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 64
ISSUE: 3
TITLE: Archives of general psychiatry
ISOABBREVIATION: Arch. Gen. Psychiatry
YEAR: 2007
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0003-990X
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Arch Gen Psychiatry
COUNTRY: United States
ISSNLINKING: 0003-990X
NLMUNIQUEID: 0372435
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Anxiety Disorders genetics
Australia epidemiology
Chromosome Mapping epidemiology
Cohort Studies epidemiology
Comorbidity epidemiology
Depressive Disorder, Major genetics
Diagnostic and Statistical Manual of Mental Disorders genetics
Diseases in Twins genetics
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Genotype genetics
Humans genetics
Linkage Disequilibrium genetics
Nerve Tissue Proteins genetics
Neurotic Disorders genetics
Pedigree genetics
Personality Disorders genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Psychiatric Status Rating Scales statistics & numerical data
Receptors, Cell Surface genetics
Semaphorins genetics
Siblings genetics
Stress, Psychological genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Nerve Tissue Proteins
0 PLXNA2 protein, human
0 Receptors, Cell Surface
0 Semaphorins
OTHER ID's