Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Li, James J.; Savage, Jeanne E.; Kendler, Kenneth S.; Hickman, Matthew; Mahedy, Liam; Macleod, John; Kaprio, Jaakko; Rose, Richard J.; Dick, Danielle M.

doi:10.15288/jsad.2017.78.442

Cited by 31 publications

(31 citation statements)

References 66 publications

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“…To determine whether the mediation models could be explained by other factors, sensitivity analyses were conducted by examining the indirect effects of the phenotypic and polygenic models of ADHD on externalizing trajectories via the effects of adolescent sensation seeking , a key marker of risk for adult substance use and externalizing outcomes and a putative intermediate phenotype (Li et al., ). Controlling for the same covariates, the models were completely consistent with the main findings.…”

Section: Resultsmentioning

confidence: 99%

Assessing phenotypic and polygenic models of ADHD to identify mechanisms of risk for longitudinal trajectories of externalizing behaviors

2019

Child Psychology Psychiatry

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Background: Children with ADHD frequently engage in higher rates of externalizing behaviors in adulthood relative to children without. However, externalizing behaviors vary across development. Little is known about how this risk unfolds across development. Phenotypic and polygenic models of childhood ADHD were used to predict individual differences in adult externalizing trajectories. Supportive parenting, school connectedness, and peer closeness were then examined as causal mechanisms. Methods: Data were from the National Longitudinal Study of Adolescent to Adult Health (N = 7,674). Externalizing behavior was measured using data from age 18 to 32 and modeled using latent class growth analysis. Child ADHD was measured using retrospective self-report (phenotypic model) and genome-wide polygenic risk scores (polygenic model). Multiple mediation models examined the direct and indirect effects of the phenotypic and polygenic models (separately) on externalizing trajectories through the effects of adolescent supportive parenting, school connectedness, and peer closeness. Results: Phenotypic and polygenic models of ADHD were associated with being in the High Decreasing (3.2% of sample) and Moderate (16.1%) adult externalizing trajectories, but not the severe Low Increasing trajectory (2.6%), relative to the Normal trajectory (78.2%). Associations between both models of ADHD on the High Decreasing and Moderate trajectories were partially mediated through the effects of school connectedness, but not supportive parenting or peer closeness. Conclusions: Findings shed light on how childhood ADHD affects downstream psychosocial processes that then predict specific externalizing outcomes in adulthood. They also reinforce the importance of fostering a strong school environment for adolescents with (and without) ADHD, as this context plays a critical role in shaping the development of externalizing behaviors in adulthood.

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Section: Resultsmentioning

confidence: 99%

Assessing phenotypic and polygenic models of ADHD to identify mechanisms of risk for longitudinal trajectories of externalizing behaviors

2019

Child Psychology Psychiatry

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“…In young adulthood, genetic influences on alcohol use vary as a function of romantic relationship status and social support networks (Barr et al, 2017). We have extended these studies to include measured polygenetic risk scores, characterizing the mediating pathways by which genetic risk is operating, and the environments that moderate associations of polygenic risk scores with adverse outcomes (Barr et al, 2019;Li et al, 2017;Salvatore et al, 2014;Salvatore et al, 2018;Savage, Salvatore et al, 2018). These studies underscore the important role of multiple environmental contexts in exacerbating or buffering the impact of genetic influences on alcohol use outcomes emerging during early adulthood.…”

Section: Genetic and Environmental Influences On Alcohol Outcomesmentioning

confidence: 99%

FinnTwin12 Cohort: An Updated Review

et al. 2019

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This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983–1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene–environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

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“…Substance use outcomes encompass nearly all of the many challenges inherent in studying complex behavioral disorders and outcomes. At the population level, they have a significant genetic component, but are also strongly influenced by the environment, 23,24,34,35 and twin studies provide further evidence that the heritability can vary considerably as a function of the environment [52][53][54][55][56][57][58][59] An environmental exposure is necessary for the development of disorder (access to and ingestion of a substance), making it a rich area for the study of gene-environment interaction (GxE). Substance use disorders are phenotypically heterogeneous, with multiple pathways of risk 60 and manifestations of the disorder.…”

Section: The Potential Of Gene Finding For Psychiatric Outcomesmentioning

confidence: 99%

“…and aggregate polygenic risk scores may impact AUDs by influencing one's subjective response to alcohol, 101 functional differences in brain reward systems 102 and personality traits like impulsivity. 57,58,103 Functional annotation of the genetic and biological processes implicated by GWAS variants 104,105 can also serve to improve our understanding of the many mechanisms leading from genes to complex behaviors.…”

Section: Understanding Mechanismmentioning

confidence: 99%

“…In adolescence, twin studies have showed that genetic influences on alcohol outcomes are higher in environments characterized by low levels of parental monitoring/knowledge 59 and higher levels of peer deviance. 54,55,57,58 Neighborhood characteristics that increase opportunity and limit control, such as a higher percentage of young adults in the neighborhood (presumably offering greater access to alcohol and social modeling), and a higher percentage of migration in and out of the community (reflecting neighborhood instability) were associated with greater genetic influences on alcohol outcomes. 53 As individuals transition into adulthood, other aspects of one's environment become more important.…”

Section: Characterizing Gene Environment Interplaymentioning

confidence: 99%

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Post‐GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

Dick

Barr

Cho

et al. 2018

Genes Brain and Behavior

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As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post-genome-wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.

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Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Cited by 31 publications

References 66 publications

Assessing phenotypic and polygenic models of ADHD to identify mechanisms of risk for longitudinal trajectories of externalizing behaviors

Assessing phenotypic and polygenic models of ADHD to identify mechanisms of risk for longitudinal trajectories of externalizing behaviors

FinnTwin12 Cohort: An Updated Review

Post‐GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

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