TY - JOUR
T1 - Examining the association of NRXN3 SNPs with borderline personality disorder phenotypes in heroin dependent cases and socio-economically disadvantaged controls
AU - Panagopoulos, Vassilis N.
AU - Trull, Timothy J.
AU - Glowinski, Anne L.
AU - Lynskey, Michael T.
AU - Heath, Andrew C.
AU - Agrawal, Arpana
AU - Henders, Anjali K.
AU - Wallace, Leanne
AU - Todorov, Alexandre A.
AU - Madden, Pamela A.F.
AU - Moore, Elizabeth
AU - Degenhardt, Louisa
AU - Martin, Nicholas G.
AU - Montgomery, Grant W.
AU - Nelson, Elliot C.
N1 - Funding Information:
This work was supported by the National Institute on Drug Abuse ( R01 DA017305 to ECN), the National Drug and Alcohol Research Centre and the Australian National Health and Medical Research Council (to LD). The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
PY - 2013
Y1 - 2013
N2 - 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: 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: 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: 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.
AB - 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: 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: 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: 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.
KW - Borderline personality disorder
KW - Genetic association study
KW - Heroin dependence
KW - NRXN3
UR - http://www.scopus.com/inward/record.url?scp=84881009148&partnerID=8YFLogxK
U2 - 10.1016/j.drugalcdep.2012.11.011
DO - 10.1016/j.drugalcdep.2012.11.011
M3 - Article
C2 - 23245376
AN - SCOPUS:84881009148
SN - 0376-8716
VL - 128
SP - 187
EP - 193
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 3
ER -