Multiple <i>OPR</i> genes influence personality traits in substance dependent and healthy subjects in two American populations

Luο, Xingguang; Zuo, Lingjun; Kranzler, Henry R.; Zhang, Huiping; Wang, Shuang

doi:10.1002/ajmg.b.30701

Cited by 25 publications

(26 citation statements)

References 41 publications

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“…For instance, Heath and colleagues(36) examined the correlation between Neuroticism and Extraversion drawn from the Eysenck Personality Questionnaire and tobacco smoking and found the associations too modest to decompose into genetic and environmental sources. Overall, findings in the current study are consistent with molecular genetic studies suggesting that personality traits and SUDs, in part, share a genetic basis (37;38) and furthermore, that personality traits may partially mediate the relationship between specific genetic polymorphisms and SUDs (39). …”

Section: Discussionsupporting

confidence: 90%

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders

et al. 2014

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Aims To examine the genetic overlap between borderline personality features (BPF) and substance use disorders (SUDs) and the extent to which variation in personality traits contributes to this covariance. Design Genetic structural equation modelling was used to partition the variance in and covariance between personality traits, BPF, and SUDs into additive genetic, shared, and individual-specific environmental factors. Setting All participants were registered with the Australian Twin Registry. Participants A total of 3,127 Australian adult twins participated in the study. Measurements Diagnoses of DSM-IV alcohol and cannabis abuse/dependence (AAD; CAD), and nicotine dependence (ND) were derived via computer-assisted telephone interview. BPF and five-factor model personality traits were derived via self-report questionnaires. Findings Genetic factors were responsible for 49% (95%CI: 42%–55%) of the variance in BPF, 38–42% (95%CI range: 32%–49%) for personality traits and 47% (95%CI: 17%–77%), 54% (95%CI: 43%–64%), and 78% (67%–86%) for ND, AAD and CAD, respectively. Genetic and individual-specific environmental correlations between BPF and SUDs ranged from .33–.56 (95%CI range: .19–.74) and .19–.32 (95%CI range: .06–.43), respectively. Overall, there was substantial support for genetic influences that were specific to AAD, ND and CAD (31%–69%). Finally, genetic variation in personality traits was responsible for 11% (Extraversion for CAD) to 59% (Neuroticism for AAD) of the correlation between BPF and SUDs. Conclusions Both genetic and individual-specific environmental factors contribute to comorbidity between borderline personality features and substance use disorders. A substantial proportion of this comorbidity can be attributed to variation in normal personality traits, particularly Neuroticism.

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Section: Discussionsupporting

confidence: 90%

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders

et al. 2014

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“…In a pharmacogenetic study of naltrexone treatment in alcohol addiction, individuals carrying the “T” allele of rs678849 had a significantly lower relapse rate after treatment compared to matched placebo controls (Gelernter et al, 2007). Another recent study by Luo et al reported an association between a haplotype including rs678849 and drug addiction in a mixed population of EA and AA cases (Luo et al, 2008). In conjunction with our findings, these results suggest that future studies designed to test the pharmacogenetic effects of rs678849 in AA CA populations are warranted.…”

Section: Discussionmentioning

confidence: 98%

Case–control association analysis of polymorphisms in the delta-opioid receptor, OPRD1, with cocaine and opioid addicted populations

Crist

Ambrose-Lanci

Vaswani

et al. 2013

Drug and Alcohol Dependence

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BACKGROUND Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The µ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR). METHODS The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations. RESULTS The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53×10−5; n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10 −7) (p-values non-FDR corrected). CONCLUSION The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.

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“…Finally, although we exclusively focused on the role of dopamine in the present analysis, a full account of the neurobiology of extraversion will ultimately need to incorporate causal inf luences from other neurochemicals, most notably pertaining to the opioid and oxytocin systems (e.g., Cardoso, Ellenbogen, Serravalle, & Linnen, 2013;Carter, 2014;Depue & Morrone-Strupinsky, 2005;Hsu et al, 2013;Luo et al, 2008;Troisi et al, 2010). Given that non-additive genetic effects seem to contribute to genetic variance in extraversion (Tellegen et al, 1988;van den Berg et al, 2014), interactions within but also between neurochemical systems are likely, if not inevitable, and constitute a further challenge for future research.…”

Section: Discussionmentioning

confidence: 99%

Trait Extraversion and Dopamine Function

Wacker

Smillie

2015

Social & Personality Psych

117

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An inf luential theory within personality neuroscience suggests that trait extraversion is underpinned by individual differences in dopamine function. In a review of the relevant literature, we evaluate this theory in light of the evidence from molecular genetics, neuroimaging, and psychopharmacology. Evidence linking individual differences in extraversion with dopamine-relevant genes, structural volume of dopamine-rich brain regions (e.g., in striatal and ventral prefrontal areas), dopamine receptor availability, and frontal alpha asymmetry is mixed at best. Evidence concerning both scalp recorded (electroencephalogram) and hemodynamic (functional magnetic resonance imaging) neural responses to rewards appears somewhat more promising. Perhaps the best evidence concerns extraversiondependent responses -both neural and behavioural -to dopaminergic drugs. Future research in this area must go beyond the demonstration of theoretically consistent associations and attempt to provide more specific causal evidence for the dopamine hypothesis of extraversion. A further challenge is to expand this hypothesis to incorporate other neurobiological processes that are likely to underlie this trait.

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Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations

Cited by 25 publications

References 41 publications

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders

Case–control association analysis of polymorphisms in the delta-opioid receptor, OPRD1, with cocaine and opioid addicted populations

Trait Extraversion and Dopamine Function

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