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PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity.

Baranger DA, Ifrah C, Prather AA, Carey CE, Corral-Frías NS, Drabant Conley E, Hariri AR, Bogdan R - Front Psychol (2016)

Bottom Line: The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity.Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli.When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant.

View Article: PubMed Central - PubMed

Affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. LouisSt. Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St. LouisSt. Louis, MO, USA.

ABSTRACT
Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions.

No MeSH data available.


Related in: MedlinePlus

PER1 rs3027172 and early life adversity interact to predict problematic drinking (ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.00438). C minor-allele carriers report increased problematic drinking behavior (AUDIT scores) in the context of early life stress (CTQ scores). The purple-shaded region denotes the regions of significance (i.e., CTQ log-transformed >3.57, equivalent to a score of 35.5).
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Figure 1: PER1 rs3027172 and early life adversity interact to predict problematic drinking (ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.00438). C minor-allele carriers report increased problematic drinking behavior (AUDIT scores) in the context of early life stress (CTQ scores). The purple-shaded region denotes the regions of significance (i.e., CTQ log-transformed >3.57, equivalent to a score of 35.5).

Mentions: There was no main effect of PER1 genotype or CTQ scores on AUDIT scores after accounting for covariates (PER1: β = 0.025, t = 0.662, p = 0.508; CTQ: β = −0.039, t = −0.983, p = 0.325; Supplemental Table 5). Initial moderation analyses found that the interaction of PER1 with ELS (CTQ scores) significantly predicted problematic drinking (ΔR2 = 0.0067, β = 0.086, t = 2.275, p = 0.023) after accounting for main effects and covariates. This interaction remained significant after accounting for 2-way interactions between covariates with PER1 rs3027172 and CTQ scores (an additional 18 covariates; ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.004; Supplemental Table 6). Post-hoc analyses revealed that minor (C) allele carriers who retrospectively reported elevated ELS (Johnson-Neyman significance for log-transformed CTQ values >3.57, = 35.5) endorsed increased problematic drinking (Figure 1). Participants were partitioned into three groups based on the distribution of CTQ-scores (low = 3.22–3.37; medium = 3.37–3.59; high = 3.59–4.08) for post-hoc examination of simple slopes. These analyses revealed that PER1 rs3027172 was associated with increased problematic drinking only in the high CTQ group (β = 1.908, t = 2.474, p = 0.014). These results are consistent with prior reports of increased heavy drinking among adolescent PER1 rs3027172 minor-allele carriers who have experienced high levels of psychosocial adversity (Dong et al., 2011). We further examined whether the PER1 × CTQ interaction predicted the likelihood of an AUDIT score over 8 (defined as the threshold for hazardous use). Logistic regression revealed that the PER1 × CTQ interaction was significantly associated with this AUDIT threshold of hazardous use (ΔR2 = 0.0087, β = 0.5908, z = 2.128, p = 0.033; Supplemental Table 7).


PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity.

Baranger DA, Ifrah C, Prather AA, Carey CE, Corral-Frías NS, Drabant Conley E, Hariri AR, Bogdan R - Front Psychol (2016)

PER1 rs3027172 and early life adversity interact to predict problematic drinking (ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.00438). C minor-allele carriers report increased problematic drinking behavior (AUDIT scores) in the context of early life stress (CTQ scores). The purple-shaded region denotes the regions of significance (i.e., CTQ log-transformed >3.57, equivalent to a score of 35.5).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814479&req=5

Figure 1: PER1 rs3027172 and early life adversity interact to predict problematic drinking (ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.00438). C minor-allele carriers report increased problematic drinking behavior (AUDIT scores) in the context of early life stress (CTQ scores). The purple-shaded region denotes the regions of significance (i.e., CTQ log-transformed >3.57, equivalent to a score of 35.5).
Mentions: There was no main effect of PER1 genotype or CTQ scores on AUDIT scores after accounting for covariates (PER1: β = 0.025, t = 0.662, p = 0.508; CTQ: β = −0.039, t = −0.983, p = 0.325; Supplemental Table 5). Initial moderation analyses found that the interaction of PER1 with ELS (CTQ scores) significantly predicted problematic drinking (ΔR2 = 0.0067, β = 0.086, t = 2.275, p = 0.023) after accounting for main effects and covariates. This interaction remained significant after accounting for 2-way interactions between covariates with PER1 rs3027172 and CTQ scores (an additional 18 covariates; ΔR2 = 0.0106, β = 0.124, t = 2.86, p = 0.004; Supplemental Table 6). Post-hoc analyses revealed that minor (C) allele carriers who retrospectively reported elevated ELS (Johnson-Neyman significance for log-transformed CTQ values >3.57, = 35.5) endorsed increased problematic drinking (Figure 1). Participants were partitioned into three groups based on the distribution of CTQ-scores (low = 3.22–3.37; medium = 3.37–3.59; high = 3.59–4.08) for post-hoc examination of simple slopes. These analyses revealed that PER1 rs3027172 was associated with increased problematic drinking only in the high CTQ group (β = 1.908, t = 2.474, p = 0.014). These results are consistent with prior reports of increased heavy drinking among adolescent PER1 rs3027172 minor-allele carriers who have experienced high levels of psychosocial adversity (Dong et al., 2011). We further examined whether the PER1 × CTQ interaction predicted the likelihood of an AUDIT score over 8 (defined as the threshold for hazardous use). Logistic regression revealed that the PER1 × CTQ interaction was significantly associated with this AUDIT threshold of hazardous use (ΔR2 = 0.0087, β = 0.5908, z = 2.128, p = 0.033; Supplemental Table 7).

Bottom Line: The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity.Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli.When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant.

View Article: PubMed Central - PubMed

Affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. LouisSt. Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St. LouisSt. Louis, MO, USA.

ABSTRACT
Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions.

No MeSH data available.


Related in: MedlinePlus