High polygenic risk scores are associated with age of onset of alcohol use disorder in adolescents and young adults at risk

The context in which drinking occurs is a critical but relatively understudied factor in alcohol use disorder (AUD) etiology. In this article, I offer a social-contextual framework for examining AUD risk by reviewing studies on the unique antecedents and deleterious consequences of social compared with solitary alcohol use in adolescents and young adults. Specifically, I provide evidence of distinct emotion regulatory functions across settings, in which social drinking is linked to enhancing positive emotions and social experiences, and solitary drinking is linked to coping with negative emotions. I end by considering the conceptual, methodological, and clinical implications of this social-contextual account of AUD risk.

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Energy Drink Consumption and the Risk of Alcohol Use Disorder among a National Sample of Adolescents and Young Adults

The Journal of Pediatrics ◽

10.1016/j.jpeds.2014.08.050 ◽

2014 ◽

Vol 165 (6) ◽

pp. 1194-1200 ◽

Cited By ~ 26

Author(s):

Jennifer A. Emond ◽

Diane Gilbert-Diamond ◽

Susanne E. Tanski ◽

James D. Sargent

Keyword(s):

Young Adults ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

Energy Drink ◽

National Sample ◽

Adolescents And Young Adults ◽

Energy Drink Consumption

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The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences

Translational Psychiatry ◽

10.1038/s41398-020-01185-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

J. L. Meyers ◽

D. B. Chorlian ◽

T. B. Bigdeli ◽

E. C. Johnson ◽

F. Aliev ◽

...

Keyword(s):

Young Adults ◽

Sex Differences ◽

Family History ◽

Collaborative Study ◽

Adolescents And Young Adults ◽

Risk Scores ◽

Eeg Coherence ◽

Neural Connectivity ◽

Polygenic Risk ◽

History Of

AbstractNeurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12–26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3–7 Hz) and alpha (7–12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15–19 (B: 0.15–0.21, p < 10–4). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.

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Genome-wide Association Study of Alcohol Consumption and Use Disorder in Multiple Populations (N = 274,424)

10.1101/527929 ◽

2019 ◽

Author(s):

Henry R. Kranzler ◽

Hang Zhou ◽

Rachel L. Kember ◽

Rachel Vickers Smith ◽

Amy C. Justice ◽

...

Keyword(s):

Alcohol Consumption ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

Genome Wide Association ◽

Risk Scores ◽

Genome Wide Association Studies ◽

Cell Type ◽

Polygenic Risk ◽

Consumption Level ◽

Genome Wide

SummaryAlthough alcohol consumption level and alcohol use disorder (AUD) diagnosis are both moderately heritable, their genetic risks and overlap are not well understood. We conducted genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores (reflecting alcohol consumption) and AUD diagnoses from electronic health records (EHRs) in a single, large multi-ancestry Million Veteran Program sample. Meta-analysis across population groups (N = 274,424) identified 18 genome-wide significant loci, 5 of which were associated with both traits and 13 with either AUDIT-C (N = 8) or AUD (N = 5). A significant genetic correlation between the traits reflects this overlap. However, downstream analyses revealed biologically meaningful points of divergence. Cell-type group partitioning heritability enrichment analyses indicated that central nervous system was the most significant cell type for AUDIT-C and the only significant cell type for AUD. Polygenic risk scores (PRS) for both traits were associated with alcohol-related disorders in two independent samples. Genetic correlations for 188 non-alcohol-related traits were significantly different for the two traits, as were the phenotypes associated with the traits’ polygenic risk scores. We conclude that EHR-derived, longitudinal, repeated measures of alcohol consumption level and AUD diagnosis can facilitate genetic discovery and help to elucidate the relationship between drinking level and AUD risk. Finally, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.

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Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

Behavior Genetics ◽

10.1007/s10519-013-9604-z ◽

2013 ◽

Vol 43 (5) ◽

pp. 386-401 ◽

Cited By ~ 12

Author(s):

David B. Chorlian ◽

Madhavi Rangaswamy ◽

Niklas Manz ◽

Jen-Chyong Wang ◽

Danielle Dick ◽

...

Keyword(s):

Young Adults ◽

Alcohol Use ◽

Age Of Onset ◽

Alcohol Use Disorders ◽

Adolescents And Young Adults

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Genome-wide investigation of alcohol response : a meta-analytic review and polygenic associations with alcohol use disorder

10.32469/10355/86474 ◽

2020 ◽

Author(s):

◽

Joseph D. Deak

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Meta Analysis ◽

Genotype Imputation ◽

Genetic Influences ◽

Risk Scores ◽

Individual Study ◽

Polygenic Risk ◽

Gene Set ◽

Genome Wide

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA AT REQUEST OF AUTHOR.] The current study aimed to extend previous genetic studies of level of response (LR) to alcohol by conducting the largest genome-wide association study (GWAS) of LR to date through the meta-analysis of multiple samples with extant SRE (Self-rating of the Effects of Alcohol) and GWAS data. A second aim was to use summary data from the described GWAS of LR to create polygenic risk scores (PRS) in an independent sample in order to determine whether, and to what extent, the genetic influences underlying LR to alcohol serve as a risk factor for alcohol use disorder (AUD). Towards these aims, datasets were processed according to standard quality control (QC) procedures allowing for genotype imputation and GWA analysis using methods appropriate for the individual study designs. Following individual study-level GWAS analysis, results were meta-analyzed utilizing an inverse-variance weighted fixed-effects model in METAL resulting in a final sample size of N=10,635. GWAS summary statistics from the SRE meta-analysis were then used to conduct gene-based and gene-set analyses, as well as compute polygenic risk scores (PRS) in an independent target sample to examine the predictive ability of the LR to alcohol PRS for DSM-IV AD symptom counts. No individual variants, genes, or gene-sets achieved study-level significance, although multiple genetic loci of interest achieved suggestive significance. The top single variant association was in an intergenic region on chromosome 2 located near the FUNDC2P2 gene (rs12463481; p=6.35x10[superscript -8]), the top gene-based association was with the PRR16 gene on chromosome 5 (p=6.72x10 [superscript -6]), and the top gene-set was with a set of genes associated with NFE2L2 targets (p=1.21 x10 [superscript -5]). No results from the PRS analysis approached significance. These findings suggest that, similar to other alcohol use outcomes, larger sample sizes will be required for the robust detection of genetic influences contributing to level of response to alcohol.

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