A Complex Interplay between Personality Domains, Marital Status and a Variant in CHRNA5 on the Risks of Cocaine, Nicotine Dependences and Cocaine-Induced Paranoia

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 = 1.54e-04 and OR = 2.12, 95%CI = 1.52-2.90, p = 4.65e-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 = 7.64e-04 and OR = 1.26, 95%CI = 1.12-1.42, p = 1.27e-03 respectively). The correlations moderated by rs16969968 were those of conscientiousness and CD (OR = 1.62, 95%CI: 1.23-2.12, p = 8.94e-04) as well as CIP (OR = 1.21, 95%CI: 1.11-1.32, p = 4.93e-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 1.67e-03. CONCLUSION The role of personality in CD and CIP may be interceded by both environment and genetics, while in ND by environment only.