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Background: Personality correlates highly with both cocaine and nicotine dependencies (CD, ND), and their co-morbid psychopathologies. However, little is known about the nature of these relationships. This study examined if environment (marriage) or genetics (a single SNP, CHRNA5* rs16969968) would moderate the correlation of personality with CD, ND and cocaine-induced paranoia (CIP) in African and European Americans (AAs, EAs).

Methods: 1432 EAs and 1513 AAs were examined using logistic regression. Personality was assessed by NEO-PI-R, while CD, ND and CIP were diagnosed according to DSM-IV. ND and CD were examined as binary traits and for the analysis of CIP, subjects were divided into 3 groups:(A) Controls with no CIP;(B) CD cases without CIP; and (C) CD cases with CIP. Multiple testing was Bonferroni-corrected.

Results: For CD and ND in the EA population, marital status proved to be a significant moderator in their relationship with openness only (OR= 1.90, 95% CI= 1.36–2.64, p= 1.54 e-04 and OR= 2.12, 95% CI= 1.52–2.90, p= 4.65 e-06 respectively). For CIP, marriage was observed to moderate its correlation with openness and neuroticism (OR= 1.39, 95% CI= 1.18–1.63, p= 7.64 e-04 and OR= 1.26, 95% CI= 1.12–1.42, p= 1.27 e-03 respectively). The correlations moderated by rs16969968 were those of conscientiousness and CD (OR= 1.62, 95% CI: 1.23–2.12, p= 8.94 e-04) as well as CIP (OR= 1.21, 95% CI: 1.11–1.32, p= 4.93 e-04 when comparing group A versus group C). No significant interactions were observed in AA population. The Bonferroni-corrected significance threshold was set to be 1.67 e-03 …