Predictive validity of genome-wide polygenic scores for alcohol use from adolescence to young adulthood

Objective: Molecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use. Methods: Latent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225).Results: The drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories. Conclusions: Higher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.

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Polygenic Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood

10.1101/2020.07.29.227439 ◽

2020 ◽

Author(s):

Joseph D. Deak ◽

D. Angus Clark ◽

Mengzhen Liu ◽

C. Emily Durbin ◽

William G. Iacono ◽

...

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Young Adulthood ◽

Externalizing Behavior ◽

Molecular Genetic ◽

Early Adulthood ◽

Predictive Utility ◽

Problematic Use ◽

Discovery Sample ◽

Polygenic Scores

AbstractObjectiveMolecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use.MethodsLatent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225).ResultsThe drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories.ConclusionsHigher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.

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Age varying polygenic effects on alcohol use in African Americans and European Americans from adolescence to adulthood

Scientific Reports ◽

10.1038/s41598-021-01923-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kit K. Elam ◽

Thao Ha ◽

Zoe Neale ◽

Fazil Aliev ◽

Danielle Dick ◽

...

Keyword(s):

Alcohol Use ◽

Association Studies ◽

Genetic Effects ◽

Risk Scores ◽

Genome Wide Association Studies ◽

Longitudinal Models ◽

Polygenic Risk ◽

Genome Wide ◽

Polygenic Scores ◽

Distal Outcome

AbstractGenetic effects on alcohol use can vary over time but are often examined using longitudinal models that predict a distal outcome at a single time point. The vast majority of these studies predominately examine effects using White, European American (EA) samples or examine the etiology of genetic variants identified from EA samples in other racial/ethnic populations, leading to inconclusive findings about genetic effects on alcohol use. The current study examined how genetic influences on alcohol use varied by age across a 15 year period within a diverse ethnic/racial sample of adolescents. Using a multi-ethnic approach, polygenic risk scores were created for African American (AA, n = 192) and EA samples (n = 271) based on racially/ethnically aligned genome wide association studies. Age-varying associations between polygenic scores and alcohol use were examined from age 16 to 30 using time-varying effect models separately for AA and EA samples. Polygenic risk for alcohol use was found to be associated with alcohol use from age 22–27 in the AA sample and from age 24.50 to 29 in the EA sample. Results are discussed relative to the intersection of alcohol use and developmental genetic effects in diverse populations.

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Predicting alcohol use from genome-wide polygenic scores, environmental factors, and their interactions in young adulthood

10.1101/2020.07.05.188656 ◽

2020 ◽

Author(s):

Radhika Kandaswamy ◽

Andrea Allegrini ◽

Alexandra F. Nancarrow ◽

Sophie Nicole Cave ◽

Robert Plomin ◽

...

Keyword(s):

Alcohol Use ◽

Environmental Factors ◽

Multiple Testing ◽

Association Studies ◽

Alcohol Use Disorders ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome ◽

Polygenic Scores ◽

Identification Test

AbstractAlcohol use during emerging adulthood is associated with adverse life outcomes but its risk factors are not well known. Here, we predicted alcohol use in 3,153 young adults aged 22 years from (a) genome-wide polygenic scores (GPS) based on genome-wide association studies for the target phenotypes number of drinks per week and Alcohol Use Disorders Identification Test scores, (b) 30 environmental factors, and (c) their interactions (i.e., GxE effects). Data was collected from 1994 to 2018 as a part of the UK Twins Early Development Study. GPS accounted for up to 1.9% of the variance in alcohol use (i.e., Alcohol Use Disorders Identification Test score), while the 30 measures of environmental factors together accounted for 21.1%. The 30 GPS-environment interactions did not explain any additional variance and none of the interaction terms exceeded the significance threshold after correcting for multiple testing. Our findings suggest that GPS and environmental factors have primarily direct, additive effects rather than interacting systematically.

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The Genetic Basis of Hypertriglyceridemia

Current Atherosclerosis Reports ◽

10.1007/s11883-021-00939-y ◽

2021 ◽

Vol 23 (8) ◽

Author(s):

Germán D. Carrasquilla ◽

Malene Revsbech Christiansen ◽

Tuomas O. Kilpeläinen

Keyword(s):

Genetic Basis ◽

Association Studies ◽

Cumulative Effect ◽

Genome Wide Association Studies ◽

Genetic Loci ◽

Risk Variants ◽

Genome Wide ◽

Severe Hypertriglyceridemia ◽

Increased Risk ◽

Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

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Predictors of Sexual Intimate Partner Violence Perpetration Among Men: A Prospective Analysis

Journal of Interpersonal Violence ◽

10.1177/0886260521989735 ◽

2021 ◽

pp. 088626052198973

Author(s):

Hailee K. Dunn ◽

Deborah N. Pearlman ◽

Madeline C. Montgomery ◽

Lindsay M. Orchowski

Keyword(s):

Intimate Partner Violence ◽

Alcohol Use ◽

Young Adulthood ◽

Partner Violence ◽

Teen Dating Violence ◽

Intimate Partner ◽

Heavy Alcohol ◽

Peer Approval ◽

Sexual Intimate Partner Violence ◽

Heavy Alcohol Use

Research demonstrates that both peer socialization and underage drinking play a significant role in teen dating violence. However, less is known about the lasting effects of these risk factors on boys’ ability to form healthy romantic relationships as they get older. The present study examined whether boys who perceived their peers would respect them more for having sex and those who engaged in past year heavy alcohol use would be more likely to perpetrate sexual intimate partner violence (IPV) in young adulthood compared to boys who did not endorse perceived peer approval for sex or report past year heavy drinking. Analyses were conducted using a sample of boys ( n = 1,189) from Waves I and III of the National Longitudinal Study of Adolescent to Adult Health (Add Health). A logistic regression was conducted to assess the relationship between perceived peer approval to have sex and heavy alcohol use at Wave I and sexual IPV at Wave III, after adjusting for demographic factors and other correlates of sexual IPV at Wave I, including age, race/ethnicity, sexual initiation in adolescence, parental attachment, annual family income, and neighborhood poverty. Boys who believed they would gain peer respect by having sex and boys who reported getting drunk in the last 12 months, regardless of how often, were significantly more likely to report sexual IPV in young adulthood compared to boys who did not endorse either of these factors. Targeting boys’ perceived peer norms regarding sexual activity and heavy alcohol use may therefore be especially important for preventing sexual IPV later in life.

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