Barr, Peter

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Dr. Barr’s background is the social determinants of mental health. After completing his doctoral training in sociology, he went on to complete a postdoctoral fellowship in psychiatric genetics at Virginia Commonwealth University. Dr Barr has advanced training in longitudinal analysis, statistical and psychiatric genetics, and the epidemiology of substance use disorders and comorbid problems. His work has explored a variety of topics including early life influences on trajectories of mental health problems, the role of social conditions in moderating genetic liability towards substance misuse, and harnessing comorbidity between psychiatric disorders to aid in genetic discovery. His recent work explores the use of social, clinical, and genetic data for clinical settings in order to identify those at extreme risk of developing various psychiatric problems. Dr Barr is part of the Externalizing Consortium and is a Co-I on an R01 from NIDA focused on using shared overlap between comorbid externalizing problems to aid in gene discovery for drug use disorders. Dr Barr is also a Co-I on the Finnish Twin Cohort (FinnTwin12) and is part of ongoing efforts to collect data from Finnish twins who are now in their early midlife.

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Now showing 1 - 10 of 37
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    PublicationOpen Access
    Polygenic risk for alcohol misuse is moderated by romantic partnerships.
    (2019-07-30) Barr, Peter; Kuo, Sally I-Chun; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Salvatore, Jessica E; Dick, Danielle M
    Background and aims: Previous twin research suggests relationship status can moderate underlying genetic liability towards alcohol misuse. This paper examined: (1) whether genome-wide polygenic scores (GPS) for alcohol consumption are associated with alcohol misuse; (2) whether these GPS are moderated by romantic relationships (gene-environment interaction; G × E) and (3) whether G × E results are consistent across sex. Design: Linear mixed-effects models were used to test associations between genome-wide polygenic scores, relationship status and alcohol use/misuse. Setting: Finnish twins born between 1983 and 1987 identified through Finland's central population registry. Participants: An intensively studied subset of Finnish Twin Study (FinnTwin12) during the young adult phase (aged 20-26 years). The analytical sample includes those with complete interview and genetic data (n = 1201). Measurements: Key measurements included involvement in a romantic partnership, drinking frequency, intoxication frequency and DSM-IV alcohol dependence (AD) symptoms. Genome-wide polygenic scores (GPS) were created from available summary statistics from a large genome-wide association study (GWAS) of drinks per week. Results: GPS predicted drinking frequency [b = 0.109; 95% confidence interval (CI) = 0.050, 0.168], intoxication frequency (b = 0.111; 95% CI = 0.054, 0.168) and AD symptoms (b = 0.123; 95% CI = 0.064, 0.182). Having a romantic relationship negatively influenced the association between GPS and drinking frequency (b = -0.105; 95% CI = -0.211, -0.001), intoxication frequency (b = -0.118; 95% CI = -0.220, -0.016) and AD symptoms (b = -0.119; 95% CI = -0.229, -0.009). There was a three-way interaction between sex, relationship status and GPS for intoxication frequency (b = 0.223; 95% CI = 0.013, 0.433), such that the reduced association between GPS and intoxication frequency for those in a relationship was only apparent in males. We found no evidence of three-way interactions for drinking frequency or AD symptoms. Conclusions: Being in a romantic relationship reduced the association between genetic predisposition and drinking, high-risk drinking and alcohol problems. However, for high-risk drinking the protective effect was limited to males, mapping onto earlier findings suggesting that males benefit more from romantic partnerships.
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    PublicationOpen Access
    Childhood socioeconomic status and longitudinal patterns of alcohol problems: Variation across etiological pathways in genetic risk.
    (2018-05-14) Barr, Peter; Silberg, Judy; Dick, Danielle M; Maes, Hermine H
    Childhood socioeconomic status (SES) is an important aspect of early life environment associated with later life health/health behaviors, including alcohol misuse. However, alcohol misuse is modestly heritable and involves differing etiological pathways. Externalizing disorders show significant genetic overlap with substance use, suggesting an impulsivity pathway to alcohol misuse. Alcohol misuse also overlaps with internalizing disorders, suggesting alcohol is used to cope. These differing pathways could lead to different patterns over time and/or differential susceptibility to environmental conditions, such as childhood SES. We examine whether: 1) genetic risk for externalizing and internalizing disorders influence trajectories of alcohol problems across adolescence to adulthood, 2) childhood SES alters genetic risk these disorders on trajectories of alcohol problems, and 3) these patterns are consistent across sex. We find modest evidence of gene-environment interaction. Higher childhood SES increases the risk of alcohol problems in late adolescence/early adulthood, while lower childhood SES increases the risk of alcohol problems in later adulthood, but only among males at greater genetic risk of externalizing disorders. Females from lower SES families with higher genetic risk of internalizing or externalizing disorders have greater risk of developing alcohol problems.
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    PublicationOpen Access
    Principal Component Analysis Reduces Collider Bias in Polygenic Score Effect Size Estimation.
    (2022-06-08) Thomas, Nathaniel S; Barr, Peter; Aliev, Fazil; Stephenson, Mallory; Kuo, Sally I-Chun; Chan, Grace; Dick, Danielle M; Edenberg, Howard J; Hesselbrock, Victor; Kamarajan, Chella; Kuperman, Samuel; Salvatore, Jessica E
    In this study, we test principal component analysis (PCA) of measured confounders as a method to reduce collider bias in polygenic association models. We present results from simulations and application of the method in the Collaborative Study of the Genetics of Alcoholism (COGA) sample with a polygenic score for alcohol problems, DSM-5 alcohol use disorder as the target phenotype, and two collider variables: tobacco use and educational attainment. Simulation results suggest that assumptions regarding the correlation structure and availability of measured confounders are complementary, such that meeting one assumption relaxes the other. Application of the method in COGA shows that PC covariates reduce collider bias when tobacco use is used as the collider variable. Application of this method may improve PRS effect size estimation in some cases by reducing the effect of collider bias, making efficient use of data resources that are available in many studies.
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    PublicationOpen Access
    Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.
    (2019-10-28) Salvatore, Jessica E; Barr, Peter; Stephenson, Mallory; Aliev, Fazil; Kuo, Sally I-Chun; Su, Jinni; Agrawal, Arpana; Almasy, Laura; Bierut, Laura; Bucholz, Kathleen; Chan, Grace; Edenberg, Howard J; Johnson, Emma C; McCutcheon, Vivia V; Meyers, Jacquelyn L; Schuckit, Marc; Tischfield, Jay; Wetherill, Leah; Dick, Danielle M
    Background and aims: The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). Design: Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Setting: Six sites in the United States. Participants: European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. Measurements: Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment. Findings: In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%). Conclusions: Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).
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    PublicationOpen Access
    Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence
    (Wiley, 2024-01-07) Lahey, Benjamin B.; Durham, E. Leighton; Brislin, Sarah J.; Barr, Peter B.; Dick, Danielle M.; Moore, Tyler M.; Pierce, Brandon L.; Tong, Lin; Reimann, Gabrielle E.; Jeong, Hee Jung; Dupont, Randolph M.; Kaczkurkin, Antonia N.
    Background: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. Methods: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Results: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. Conclusions: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.
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    PublicationOpen Access
    The Associations of Polygenic Scores for Risky Behaviors and Parenting Behaviors with Adolescent Externalizing Problems.
    (2021-07-31) Ksinan, Albert J; Smith, Rebecca L; Barr, Peter; Vazsonyi, Alexander T
    The current study focused on longitudinal effects of genetics and parental behaviors and their interplay on externalizing behaviors in a panel study following individuals from adolescence to young adulthood. The nationally representative sample of Add Health participants of European ancestry included N = 4142 individuals, measured on three occasions. Parenting was operationalized as experiences with child maltreatment and maternal closeness. Externalizing problems were operationalized as alcohol use, cannabis use, and antisocial behaviors. Genetic effects were operationalized as a polygenic score (PGS) of risky behaviors. The results showed significant effects for child maltreatment, maternal closeness, and PGS, above and beyond other factors and previous levels of externalizing behaviors. Furthermore, maternal closeness was found to negatively correlate with PGS. No significant interaction effects of parenting and PGS were found. The results underscore the joint independent effects of parenting and genetics on the change in externalizing behaviors from adolescence to young adulthood.
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    PublicationOpen Access
    Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans.
    (2022-08-07) Aliev, Fazil; Barr, Peter; Davies, Andrew G; Dick, Danielle M; Bettinger, Jill C
    Background: Individual variation in the physiological response to alcohol is predictive of an individual's likelihood to develop alcohol use disorder (AUD). Evidence from diverse model organisms indicates that the levels of long-chain polyunsaturated omega-3 fatty acids (ω-3 LC-PUFAs) can modulate the behavioral response to ethanol and therefore may impact the propensity to develop AUD. While most ω-3 LC-PUFAs come from diet, humans can produce these fatty acids from shorter chain precursors through a series of enzymatic steps. Natural variation in the genes encoding these enzymes has been shown to affect ω-3 LC-PUFA levels. We hypothesized that variation in these genes could contribute to the susceptibility to develop AUD. Methods: We identified nine genes (FADS1, FADS2, FADS3, ELOVL2, GCKR, ELOVL1, ACOX1, APOE, and PPARA) that are required to generate ω-3 LC-PUFAs and/or have been shown or predicted to affect ω-3 LC-PUFA levels. Using both set-based and gene-based analyses we examined their association with AUD and two AUD-related phenotypes, alcohol consumption, and an externalizing phenotype. Results: We found that the set of nine genes is associated with all three phenotypes. When examined individually, GCKR, FADS2, and ACOX1 showed significant association signals with alcohol consumption. GCKR was significantly associated with AUD. ELOVL1 and APOE were associated with externalizing. Conclusions: Taken together with observations that dietary ω-3 LC-PUFAs can affect ethanol-related phenotypes, this work suggests that these fatty acids provide a link between the environmental and genetic influences on the risk of developing AUD.
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    PublicationOpen Access
    A Family-Based Genome Wide Association Study of Externalizing Behaviors.
    (2020-04-01) Barr, Peter; Salvatore, Jessica E; Wetherill, Leah; Anokhin, Andrey; Chan, Grace; Edenberg, Howard J; Kuperman, Samuel; Meyers, Jacquelyn; Nurnberger, John; Porjesz, Bernice; Schuckit, Mark; Dick, Danielle M
    Shared genetic factors contribute to the high degree of comorbidity among externalizing problems (e.g. substance use and antisocial behavior). We leverage this common genetic etiology to identify genetic influences externalizing problems in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7568; African ancestry = 3274). We performed a family-based genome-wide association study (GWAS) on externalizing scores derived from criterion counts of five DSM disorders (alcohol dependence, alcohol abuse, illicit drug dependence, illicit drug abuse, and either antisocial personality disorder or conduct disorder). We meta analyzed these results with a similar measure of externalizing in an independent sample, Spit for Science (combined sample N = 15,112). We did not discover any robust genome-wide significant signals. Polygenic scores derived from the ancestry-specific GWAS summary statistics predicted externalizing problems in an independent European ancestry sample, but not in those of African ancestry. However, these PRS were no longer significant after adjusting for multiple testing. Larger samples with deep phenotyping are necessary for the discovery of SNPs related to externalizing problems.
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    PublicationOpen Access
    Exploring the relationships between adolescent alcohol misuse and later life health outcomes.
    (2022-09-17) Pascale, Angela; Stephenson, Mallory; Barr, Peter; Latvala, Antti; Aaltonen, Sari; Piirtola, Maarit; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Maes, Hermine; Dick, Danielle M; Salvatore, Jessica E
    Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self-rated health (β = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (β = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.
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    PublicationOpen Access
    Neighborhood conditions and trajectories of alcohol use and misuse across the early life course.
    (2018-03-05) Barr, Peter
    While neighborhood conditions have been linked to alcohol misuse, less is known about the long-term consequences of exposure to adverse neighborhood conditions early in the life course. Using data from the National Longitudinal Survey of Adolescent to Adult Health, we examined how trajectories of alcohol behaviors from ages 12 to 32 varied according to neighborhood disorder, disadvantage, and advantage. Early exposure to adverse neighborhood conditions placed individuals at greater risk of being a current drinker and alcohol misuse, though these individuals never reached the same levels as those in more stable, advantaged neighborhoods. Early exposure appears to place individuals at risk for alcohol misuse across the early life course.