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
23245376
TITLE
Examining the association of NRXN3 SNPs with borderline personality disorder phenotypes in heroin dependent cases and socio-economically disadvantaged controls.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Borderline personality disorder (BPD) and substance use disorders frequently co-occur; their dual presence predicts poor prognosis. The genetic underpinnings of BPD have not been well-characterized and could offer insight into comorbidity. The current report focuses on the association of neurexin 3 (NRXN3) single nucleotide polymorphisms (SNPs) with BPD symptoms in heroin dependent cases and controls.
METHODS NlmCategory: METHODS
The sample of the Comorbidity and Trauma Study, a genetic association study of heroin dependence, consists of Australian heroin dependent cases ascertained from opioid replacement therapy clinics and controls ascertained in nearby economically disadvantaged neighborhoods. The assessment included a screening instrument for BPD, used previously in Australian population surveys. Genotypic and BPD phenotypic data were available for 1439 cases and 507 controls. We examined the association of 1430 candidate gene SNPs with BPD phenotypes.
RESULTS NlmCategory: RESULTS
One or more NRXN3 SNPs were nominally associated with all BPD phenotypes; however, none met the conservative significance threshold we employed to correct for multiple testing. The most strongly associated SNPs included rs10144398 with identity disturbance (p=4.9×10(-5)) and rs10151731 with affective instability (p=8.8×10(-5)). The strongest association with screening positive for BPD was found for the NRXN3 SNP, rs10083466 (p=.0013). Neither the correlation of BPD phenotypes nor the linkage disequilibrium relationships of the SNPs account for the number of observed associations involving NRXN3 SNPs.
CONCLUSIONS NlmCategory: CONCLUSIONS
Our findings provide intriguing preliminary evidence for the association of NRXN3 with BPD phenotypes. The strongest associations were found for traits (i.e., affective instability; identity disturbance) also observed with other disorders.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
DATE PUBLISHED
2013 Mar 1
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/06/27
revised 2012/11/15
accepted 2012/11/16
aheadofprint 2012/12/12
entrez 2012/12/19 06:00
pubmed 2012/12/19 06:00
medline 2013/08/06 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Panagopoulos VN Panagopoulos Vassilis N VN Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO 63110, USA.
Trull TJ Trull Timothy J TJ
Glowinski AL Glowinski Anne L AL
Lynskey MT Lynskey Michael T MT
Heath AC Heath Andrew C AC
Agrawal A Agrawal Arpana A
Henders AK Henders Anjali K AK
Wallace L Wallace Leanne L
Todorov AA Todorov Alexandre A AA
Madden PA Madden Pamela A F PA
Moore E Moore Elizabeth E
Degenhardt L Degenhardt Louisa L
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Nelson EC Nelson Elliot C EC
INVESTIGATORS
JOURNAL
VOLUME: 128
ISSUE: 3
TITLE: Drug and alcohol dependence
ISOABBREVIATION: Drug Alcohol Depend
YEAR: 2013
MONTH: Mar
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1879-0046
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Drug Alcohol Depend
COUNTRY: Ireland
ISSNLINKING: 0376-8716
NLMUNIQUEID: 7513587
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
K05 AA017688 NIAAA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Australia
Borderline Personality Disorder genetics
Case-Control Studies genetics
Female genetics
Genotype genetics
Heroin Dependence genetics
Humans genetics
Logistic Models genetics
Male genetics
Middle Aged genetics
Nerve Tissue Proteins genetics
Opiate Substitution Treatment genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Principal Component Analysis genetics
Psychiatric Status Rating Scales genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Nerve Tissue Proteins
0 neurexin IIIalpha
OTHER ID's
OTHERID SOURCE
NIHMS429608 NLM
PMC3832348 NLM