Danielle M Dick

Virginia Commonwealth University, Ричмонд, Virginia, United States

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Publications (206)832.03 Total impact

  • Jessica E. Salvatore, Danielle M. Dick
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    ABSTRACT: The idea that both genetic and environmental influences contribute to behavioral outcomes is widely accepted. However, the practice of examining candidate Gene × Environment interaction (cGxE) is controversial. In this article, we summarize some of the key issues involved in cGxE research and provide recommendations for work in this area. Highlighted challenges include the selection of the gene, the development of the cGxE hypothesis, and the coding of the genotype. To address these challenges and gain confidence in cGxE findings, we recommend using empirical data to select and code genes/variants, using theory to develop cGxE hypotheses and a rigorous and transparent approach to hypothesis testing. Family researchers have much to offer to the study of Gene × Environment research in view of their process-oriented theories that are grounded in decades of nuanced measurement of the environment; implementing these best practices will help deliver on that promise.
    Journal of Marriage and Family 04/2015; 77(2). DOI:10.1111/jomf.12164 · 3.01 Impact Factor
  • Kenneth S Kendler, John Myers, Danielle Dick
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    ABSTRACT: Peer group deviance (PGD) is strongly associated with current and future externalizing behaviors. Debate remains about the degree to which this association arises from social selection. The first year of university constitutes a social experiment in which most individuals leave their home environment and recreate for themselves a new peer group. PGD was measured in newly arrived university students and then 6 and 18 months later. Other personality and family traits were also assessed. PGD reported for high school friends at the start of university and university friends 6 months later were substantially correlated (+0.60). This correlation was only slightly diminished if restricted to students whose home was greater than 50 miles from the university. PGD was strongly predicted across three cohorts by male sex (+), extraversion (+), conscientiousness (-), a family history of alcohol use disorders (+) and depression (+), and religiosity (-).These predictors of PGD had a relatively stable impact over 18 months and, aside from sex, differed only modestly in males and females. As individuals change social groups from high school to university, the level of PGD remains relatively stable, suggesting that individuals play a strong role in selecting peer groups with consistent characteristics. PGD is also predicted cross-sectionally and longitudinally by personality, family background and religiosity. Our results suggest that the association between personal and peer deviance is due at least in part to the effects of social selection.
    Social Psychiatry and Psychiatric Epidemiology 02/2015; DOI:10.1007/s00127-015-1031-4 · 2.58 Impact Factor
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    ABSTRACT: This study examined whether relocating from a high-poverty neighborhood to a lower poverty neighborhood as part of a federal housing relocation program (HOPE VI; Housing Opportunities for People Everywhere) had effects on adolescent mental and behavioral health compared to adolescents consistently living in lower poverty neighborhoods. Sociodemographic, risk behavior, and neighborhood data were collected from 592 low-income, primarily African-American adolescents and their primary caregivers. Structured psychiatric interviews were conducted with adolescents. Prerelocation neighborhood, demographic, and risk behavior data were also included. Hierarchical Linear Modeling (HLM) was used to test associations between neighborhood variables and risk outcomes. HLM was used to test whether the effect of neighborhood relocation and neighborhood characteristics might explain differences in sexual risk taking, substance use, and mental health outcomes. Adolescents who relocated of HOPE VI neighborhoods (n = 158) fared worse than control group participants (n = 429) on most self-reported mental health outcomes. The addition of subjective neighborhood measures generally did not substantively change these results. Our findings suggest that moving from a high-poverty neighborhood to a somewhat lower poverty neighborhood is not associated with better mental health and risk behavior outcomes in adolescents. The continued effects of having grown up in a high-poverty neighborhood, the small improvements in their new neighborhoods, the comparatively short length of time they lived in their new neighborhood, and/or the stress of moving appears to worsen most of the mental health outcomes of HOPE VI compared to control group participants who consistently lived in the lower poverty neighborhoods. © 2015 Association for Child and Adolescent Mental Health.
    Journal of Child Psychology and Psychiatry 02/2015; DOI:10.1111/jcpp.12386 · 5.67 Impact Factor
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    ABSTRACT: We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants' risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention.
    Development and Psychopathology 02/2015; 27(1):81-95. DOI:10.1017/S095457941400131X · 4.40 Impact Factor
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    ABSTRACT: Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.
    Perspectives on Psychological Science 01/2015; 10(1):37-59. DOI:10.1177/1745691614556682 · 4.89 Impact Factor
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    ABSTRACT: Objective: The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult individuals (N = 2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman's Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability. Method: We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes. Results: For all phenotypes, there was significant enrichment of association results (p < .05) compared with chance expectations. The greatest number of significant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p < .05 with Sensation Seeking was significantly greater than that observed for each of the other phenotypes. Conclusions: We find evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we find significant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems. (J. Stud. Alcohol Drugs, 76, 38-46, 2015).
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    ABSTRACT: Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.
    Journal of Policy Analysis and Management 01/2015; DOI:10.1002/pam.21811 · 0.93 Impact Factor
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    ABSTRACT: AimsAlcohol problems (AP) contribute substantially to the global disease burden. Twin and family studies suggest that AP are genetically influenced, though few studies have identified variants or genes that are robustly associated with risk. This study identifies genetic and genomic influences on AP during young adulthood, which is often when drinking habits are established.DesignWe conducted a genome-wide association study of AP. We further conducted gene-based tests, gene ontology analyses, and functional genomic enrichment analyses to assess genomic factors beyond single variants that are relevant to AP.SettingThe Avon Longitudinal Study of Parents and Children, a large population-based study of a UK birth cohort.ParticipantsGenetic and phenotypic data were available for 4304 participants.MeasurementsThe AP phenotype was a factor score derived from items from the Alcohol Use Disorders Identification Test, symptoms of DSM-IV alcohol dependence, and three additional problem-related items.FindingsOne variant met genome-wide significance criteria. Four out of 22,880 genes subjected to gene-based analyses survived a stringent significance threshold (q < .05); none of these have been previously implicated in alcohol-related phenotypes. Several biologically plausible gene ontologies were statistically over-represented among implicated SNPs. SNPs on the Illumina 550 K SNP chip accounted for ~5% of the phenotypic variance in AP.Conclusions Genetic and genomic factors appear to play a role in alcohol problems in young adults. Genes involved in nervous system-related processes, such as signal transduction and neurogenesis, potentially contribute to liability to alcohol problems, as do genes expressed in non-brain tissues. This article is protected by copyright. All rights reserved.
    Addiction 12/2014; DOI:10.1111/add.12822 · 4.60 Impact Factor
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    ABSTRACT: Background Alcohol-related blackouts (ARBs) are reported by ~50% of drinkers. While much is known about the prevalence of ARBs in young adults and their cross-sectional correlates, there are few prospective studies regarding their trajectories over time during mid-adolescence. This paper reports latent trajectory classes of ARBs between age 15 and 19, along with predictors of those patterns.Methods Latent class growth analysis (LCGA) was used to evaluate the pattern of occurrence of ARBs across 4 time points for 1,402 drinking adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multinomial regression analyses evaluated age-15 demography, substance-related items, externalizing characteristics, and estimated peer substance use as predictors of latent class membership.ResultsARBs were reported at age 15 in 30% and at age 19 in 74% of these subjects. Four latent trajectory classes were identified: Class 1 (5.1%) reported no blackouts; for Class 2 (29.5%), ARBs rapidly increased with age; for Class 3 (44.9%), blackouts slowly increased; and for Class 4 (20.5%), ARBs were consistently reported. Using Class 2 (rapid increasers) as the reference, predictors of class membership included female sex, higher drinking quantities, smoking, externalizing characteristics, and estimated peer substance involvement (pseudo R2 = 0.22).ConclusionsARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics.
    Alcoholism Clinical and Experimental Research 12/2014; DOI:10.1111/acer.12601 · 3.31 Impact Factor
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    ABSTRACT: Background Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother–sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences.Methods We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n = 1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders (AUD-GR) was indexed by his/her parents' and cotwin's DSM-IV Alcohol Dependence (AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders (EXT-GR) was indexed with a composite measure of parents' and cotwin's DSM-IV Conduct Disorder and Antisocial Personality Disorder criterion counts.ResultsEXT-GR was most strongly related to alcohol use behaviors during adolescence, while AUD-GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD-GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT-GR influenced age 22 AD more in males than in females. In addition, the associations of AUD-GR and EXT-GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers.Conclusions We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD-GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT-GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins.
    Alcoholism Clinical and Experimental Research 11/2014; 38(11). DOI:10.1111/acer.12560 · 3.31 Impact Factor
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    ABSTRACT: Objective: Alcohol use and internalizing problems are often positively associated during adolescence and adulthood. However, the basis of this relationship remains poorly understood, and longitudinal data collected in population-based samples could improve the development of etiological models. Method: Using a prospective population-based U.K. cohort, the current study examined the relationship between frequency of drinking during adolescence (ages 13-15, N = 7,100) with problems with depression and anxiety at average age 17 years 10 months (n = 4,292). Analyses were conducted separately by sex and adjusted by the inclusion of potential individual- and familial-level confounders. Results: Among boys, drinking frequency was positively associated with later depression but not anxiety. This association was robust to adjustment for covariates/confounders. Among girls, drinking frequency was related to later depression and anxiety in univariable analyses. In multivariable analyses, only the association with depression remained after adjustment for covariates/confounders. Results were comparable across sexes, although the effect size of drinking frequency was higher among boys. Conclusions: Higher adolescent alcohol use, even at sub-clinical levels, is associated with an increased risk of later problems with depression but may not be associated with an aggregate measure of anxiety. Future research should consider the possibility of differential relationships between multiple measures of adolescent alcohol use and distinct internalizing outcomes later in development. (J. Stud. Alcohol Drugs, 75, 758-765, 2014).
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    ABSTRACT: Background Adolescent drinking is an important public health concern, one that is influenced by both genetic and environmental factors. The functional variant rs1229984 in alcohol dehydrogenase 1B (ADH1B) has been associated at a genome-wide level with alcohol use disorders in diverse adult populations. However, few data are available regarding whether this variant influences early drinking behaviors and whether social context moderates this effect. This study examines the interplay between rs1229984 and peer drinking in the development of adolescent drinking milestones.Methods One thousand five hundred and fifty European and African American individuals who had a full drink of alcohol before age 18 were selected from a longitudinal study of youth as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Cox proportional hazards regression, with G × E product terms in the final models, was used to study 2 primary outcomes during adolescence: age of first intoxication and age of first DSM-5 alcohol use disorder symptom.ResultsThe minor A allele of rs1229984 was associated with a protective effect for first intoxication (HR = 0.56, 95% CI 0.41 to 0.76) and first DSM-5 symptom (HR = 0.45, 95% CI 0.26 to 0.77) in the final models. Reporting that most or all best friends drink was associated with a hazardous effect for first intoxication (HR = 1.81, 95% CI 1.62 to 2.01) and first DSM-5 symptom (HR = 2.17, 95% 1.88 to 2.50) in the final models. Furthermore, there was a significant G × E interaction for first intoxication (p = 0.002) and first DSM-5 symptom (p = 0.01). Among individuals reporting none or few best friends drinking, the ADH1B variant had a protective effect for adolescent drinking milestones, but for those reporting most or all best friends drinking, this effect was greatly reduced.Conclusions Our results suggest that the risk factor of best friends drinking attenuates the protective effect of a well-established ADH1B variant for 2 adolescent drinking behaviors. These findings illustrate the interplay between genetic and environmental factors in the development of drinking milestones during adolescence.
    Alcoholism Clinical and Experimental Research 09/2014; 38(10). DOI:10.1111/acer.12524 · 3.31 Impact Factor
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    ABSTRACT: AbstractBackground The age at onset of alcohol dependence (AD) is a critical moderator of genetic associations for alcohol dependence. The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA). Methods Genomewide SNP genotyping was performed in 1788 regular drinkers from 118 large European American families densely affected with alcoholism. We used a genome-wide Cox proportional hazards regression model to test for association between age at onset of AD and SNPs. Results This family-based analysis identified an intergenic SNP, rs2168784 on chromosome 3 that showed strong evidence of association (p= 5 × 10−9) with age at onset of AD among regular drinkers. Carriers of the minor allele of rs2168784 had 1.5 times the hazard of AD onset as compared with those homozygous for the major allele. By the age of 20 years, nearly 30% of subjects homozygous for the minor allele were alcohol dependent while only 19% of those homozygous for the major allele were. We also identified intronic SNPs in the ADP-ribosylation factor like 15 (ARL15) gene on chromosome 5 (P = 1.11 × 10−8) and the UTP20 small subunit (UTP20) gene on chromosome 12 (P = 4.32 × 10−8) that were associated with age at onset of AD. Conclusions This extended family based genome-wide cox-proportional hazards analysis identified several loci that might be associated with age at onset of AD.
    Drug and Alcohol Dependence 09/2014; DOI:10.1016/j.drugalcdep.2014.05.023 · 3.28 Impact Factor
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    ABSTRACT: Depressive symptoms and alcohol misuse contribute substantially to the global health burden. These phenotypes often manifest, and frequently co-occur, during adolescence. However, few studies have examined whether both baseline levels of depressive symptoms and change in symptoms are associated with alcohol outcomes. In addition, inconsistent findings could be due to sex differences or the use of different alcohol outcomes. Using data from a prospective population-based cohort in the UK, we estimated trajectories of depressive symptoms from 12 years 10 months to 17 years 10 months, separately for male and female participants. We assessed whether baseline and change in depressive symptoms were associated with use and harmful use of alcohol at 18 years 8 months. Among females, increasing depressive symptoms were associated with increased alcohol use; whilst for males, there was little evidence of this. When examining harmful levels of alcohol use, baseline levels of depressive symptoms in males were weakly related to later harmful alcohol use but this association was attenuated substantially through adjustment for confounders. In contrast, both baseline symptoms and increase in symptoms were associated with later harmful alcohol use in females and these associations were not diminished by confounder adjustment. Elevated depressive symptoms during adolescence are positively associated with increases in both use and harmful use of alcohol at 18 years 8 months. These findings differ between the sexes. Further research is needed to examine the mechanisms underlying the link between depressive symptoms and harmful alcohol use to identify potentially modifiable factors for intervention.
    European Child & Adolescent Psychiatry 08/2014; DOI:10.1007/s00787-014-0600-5 · 3.55 Impact Factor
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    ABSTRACT: Objective: We examined the associations between romantic relationship status and alcohol use and problems in a large sample of first-year college students. Method: Participants (n = 2,056) came from a longitudinal study of college students who answered questions about relationship status (single, in an exclusive relationship, or dating several people), alcohol use, and alcohol problems at two time points across their first year. Results: After we controlled for a number of covariates (parental alcohol problems, high school conduct problems, peer deviance, and extraversion), we found that dating several people was associated with higher alcohol use and problems, compared with being single or being in an exclusive relationship, at the follow-up assessment only, with modest effect sizes. Being in an exclusive relationship was not associated with lower alcohol use or problems compared with being single. Relationship dissolution was associated with a modest longitudinal increase in alcohol problems. Conclusions: It is important to consider alternative relationship statuses (e.g., dating several people) for understanding the association of romantic status with alcohol use and problems in college-aged samples. Involvement in an exclusive romantic relationship (vs. being single) in this age group is not associated with the behavioral health benefits documented in older-adult samples. College students dating several people may be at risk for high levels of alcohol use or problems and may benefit from targeted interventions. Those who have recently experienced a breakup also may be at risk for increases in alcohol problems, although the clinical relevance of this finding should be tempered by the small observed effect size. (J. Stud. Alcohol Drugs, 75, 580-589, 2014).
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    ABSTRACT: Objective: Prior studies of the relationship between socioeconomic status (SES) and alcohol consumption and problems in adolescence have been inconclusive. Few studies have examined all three major SES indicators and a broad range of alcohol-related outcomes at different ages. Method: In the Avon Longitudinal Study of Parents and Children cohort, we examined (by logistic regression, with differential weighting to control for attrition) the relationship between family income and parental education and occupational status, and five alcohol outcomes assessed at ages 16 and 18 years. Results: At age 16, high SES-as indexed by income and education-significantly predicted frequent alcohol consumption. Low SES-as measured by education and occupational status-predicted alcohol-related problems. At age 18, high SES-particularly income and education-significantly predicted frequent alcohol consumption and heavy episodic drinking and, more weakly, symptoms of alcohol dependence. All three measures of SES were inversely related to high-quantity consumption and alcohol behavioral problems. Conclusions: In adolescents in the United Kingdom, the relationship between SES and alcohol-related behaviors is complex and varies as a function of age, SES measure, and specific outcome. High SES tends to predict increased consumption and, in later adolescence, heavy episodic drinking and perhaps symptoms of alcohol dependence. Low SES predicts alcohol-related behavioral problems and, in later adolescence, high-quantity alcohol consumption. (J. Stud. Alcohol Drugs, 75, 541-545, 2014).
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    ABSTRACT: In order to further understand why depressive symptoms are associated with negative goal appraisals, the present study examined the genetic and environmental correlations and interactions between depressive symptoms and career-related goal appraisals. A total of 1,240 Finnish twins aged 21-26 years completed a questionnaire containing items on the appraisal of their career goals along five dimensions: importance, progress, effort, strain, and self-efficacy. In the same questionnaire, the 10-item General Behavior Inventory assessed depressive symptoms. Structural equation modeling was used to evaluate the genetic and environmental correlations and gene-environment interactions between the career-goal appraisals and depressive symptoms. Associations were identified, and were attributed to environmental factors. Of the career-related goal appraisals, the shared environmental component was of a higher magnitude for the dimension of strain among the depressed compared with non-depressed subjects. The results indicate that the interplay between depressive symptoms and negative career-related goal appraisals is significantly affected by environmental factors, and thus possibly susceptible to targeted interventions.
    Twin Research and Human Genetics 06/2014; 17(4):1-8. DOI:10.1017/thg.2014.33 · 1.92 Impact Factor
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    ABSTRACT: The co-occurrence of alcohol use and antisocial behavior is well established, but different hypotheses exist regarding the direction of effects between the 2 behaviors. We used longitudinal data to examine the directional relationship between the 2 behaviors across adolescence.
    Alcoholism Clinical and Experimental Research 06/2014; DOI:10.1111/acer.12446 · 3.31 Impact Factor
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    ABSTRACT: Background In a community sample of low-income African American adolescents, we tested the interactive effects of variation in the mu 1 opioid receptor (OPRM1) gene and the occurrence of stressful life events on symptoms of depression. Method Interactive effects of 24 OPRM1 simple nucleotide polymorphisms (SNP) and adolescent report of stressful life events on depression were tested using multilevel regressions. SNPs were dummy coded to test both additive and dominate forms of coding. Results Five OPRM1 SNPs showed significant evidence of interaction with stressful life events to alter depression risk (or symptoms) after adjusting for multiple testing and the correlated nature of the SNPs. Follow-up analyses showed significant differences based on OPRM1 genotype at both lower and higher frequencies of stressful life events, suggesting that participants with a copy of the minor allele on OPRM1 SNPs rs524731, rs9478503, rs3778157, rs10485057, and rs511420 have fewer symptoms in low stress conditions but more symptoms in high stress conditions compared to major allele homozygotes. Limitations The genetic variants associated with depression in African American adolescents may not translate to other ethnic groups. This study is also limited in that only one gene that functions within a complex biological system is addressed. Conclusions This current study is the first to find an interaction between OPRM1 and life stress that is associated with depression. It also addressed an understudied population within the behavioral genetics literature. Further research should test additional genes involved in the opioid system and expand the current findings to more diverse samples.
    Journal of Affective Disorders 06/2014; 162:12–19. DOI:10.1016/j.jad.2014.03.020 · 3.76 Impact Factor
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    ABSTRACT: Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems-derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)-predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07-0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes.
    06/2014; 5(2):330-46. DOI:10.3390/genes5020330

Publication Stats

6k Citations
832.03 Total Impact Points

Institutions

  • 2008–2015
    • Virginia Commonwealth University
      • • Virginia Institute for Psychiatric and Behavioral Genetics
      • • Department of Psychiatry
      Ричмонд, Virginia, United States
    • Washington School of Psychiatry
      Washington, Washington, D.C., United States
    • University of Jyväskylä
      • Department of Psychology
      Jyväskylä, Province of Western Finland, Finland
  • 2010–2013
    • National Institute for Health and Welfare, Finland
      • Department of Mental Health and Substance Abuse Services (MHSA)
      Helsinki, Uusimaa, Finland
    • University of Amsterdam
      • Department of Education
      Amsterdamo, North Holland, Netherlands
    • UConn Health Center
      • Department of Psychiatry
      Farmington, CT, United States
  • 2004–2013
    • Washington University in St. Louis
      • • Department of Psychiatry
      • • Department of Psychology
      Saint Louis, MO, United States
  • 2012
    • University of Colorado at Boulder
      • Institute for Behavioral Genetics (IBG)
      Boulder, CO, United States
  • 2000–2012
    • Indiana University Bloomington
      • Department of Psychological and Brain Sciences
      Bloomington, IN, United States
  • 2008–2010
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2002–2010
    • Indiana University-Purdue University Indianapolis
      • • Department of Chemistry and Chemical Biology
      • • Department of Biochemistry and Molecular Biology
      • • Department of Medical and Molecular Genetics
      Indianapolis, IN, United States
  • 2009
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, CA, United States
  • 2001–2008
    • University of Helsinki
      • Department of Dental Public Health
      Helsinki, Province of Southern Finland, Finland
    • Indiana University Health
      Bloomington, Indiana, United States
  • 2003–2005
    • Indiana University-Purdue University School of Medicine
      • Institute of Psychiatric Research
      Indianapolis, Indiana, United States