Symposium
Session Room: Carron
Session Room: Carron
Saturday, June 27, 05:40 PM – 06:55 PM
SCNP-Selected Symposium 10:
From Genomes to Behavior: Mapping Risk Pathways in Addiction and Mental Health
From Genomes to Behavior: Mapping Risk Pathways in Addiction and Mental Health
This symposium examines how genetic and environmental factors contribute to substance use disorders (SUDs), their psychiatric comorbidities, and downstream impacts on health-related behaviors. Using data from large international cohorts and advanced statistical tools, the speakers will explore shared genetic liability across disorders, the interaction between environmental context and genetic predisposition, and how inherited risk translates into real-world patterns of medication use and healthcare engagement.
Dr Ole Andreassen will discuss evidence for shared genetic architecture between psychiatric disorders and SUDs, based on genome-wide analyses from large international samples and novel analytical tools. For alcohol use disorders (AUD), they found positive genetic correlations and extensive shared genetic architecture between AUD and mental traits and disorders, suggesting shared genetic liability.[1] Genetic loci involved in the genetic overlap implicate striatum, hypothalamus, and prefrontal cortex as brain regions with genetic enrichment. Further analysis implicated potential drug targets (GABAergic, dopaminergic and serotonergic receptors). Together with results from other SUDs, genetic factors are involved in the comorbidity between SUDs and mental disorders. However, the polygenic risk scores (PRS) from these studies are not yet accurate enough to provide clinically relevant predictions.
Dr Joel Gelernter will present data from his group concerning genetic and nongenetic predictors of AUD risk,[2] quantifying contributions of environmental and genetic factors to AUD across different ancestries. In over 11,000 individuals of European (EUR) and African (AFR) ancestry from the Yale-Penn study, PRSs for problematic alcohol use (PAU) were positively associated with AUD criterion count in both ancestries, and predicted 1.9% of AUD criterion count in EUR and 1.3% in AFR. A combination of education, substance use in the household before age 13, annual household income, and male sex explained 73% of the variance in AUD criterion count in AFR and 59% in EUR sample. Thus, in both populations, environmental factors explained most of the explicable variance in AUD criterion count, but PRS was also a statistically significant predictor. Data pertaining to other SUDs will be presented as well.
Dr Michal Graczyk will explore how genetic vulnerability to addiction manifests in real-world healthcare behaviours, drawing on data from over 377,000 UK Biobank participants.[3] He found that PRS for five SUDs (alcohol, tobacco, cocaine, opioids, cannabis)[4-6] associated with increased prescription medication use and healthcare contacts. In a phenome-wide study across 260 medications, individuals with higher SUD PRSs were more likely to use not only medications with abuse potential (e.g. opioids, gabapentinoids) but also medications not typically considered addictive but linked to medical morbidity (e.g. vasodilators). Substance-specific patterns emerged for a few classes, such as hypnotics in relation alcohol and opioid use disorder PRS. Mendelian randomization analyses further supported causal pathways from drug and tobacco use to regular use of non-opioid analgesics and antidepressants. These findings extend our understanding of addiction genetics by linking inherited risk to broader health system impacts.
Together, these presentations illustrate how genetic and environmental risk factors contribute not only to the development of psychiatric and substance use disorders, but also to broader patterns of healthcare behaviours.
Dr Ole Andreassen will discuss evidence for shared genetic architecture between psychiatric disorders and SUDs, based on genome-wide analyses from large international samples and novel analytical tools. For alcohol use disorders (AUD), they found positive genetic correlations and extensive shared genetic architecture between AUD and mental traits and disorders, suggesting shared genetic liability.[1] Genetic loci involved in the genetic overlap implicate striatum, hypothalamus, and prefrontal cortex as brain regions with genetic enrichment. Further analysis implicated potential drug targets (GABAergic, dopaminergic and serotonergic receptors). Together with results from other SUDs, genetic factors are involved in the comorbidity between SUDs and mental disorders. However, the polygenic risk scores (PRS) from these studies are not yet accurate enough to provide clinically relevant predictions.
Dr Joel Gelernter will present data from his group concerning genetic and nongenetic predictors of AUD risk,[2] quantifying contributions of environmental and genetic factors to AUD across different ancestries. In over 11,000 individuals of European (EUR) and African (AFR) ancestry from the Yale-Penn study, PRSs for problematic alcohol use (PAU) were positively associated with AUD criterion count in both ancestries, and predicted 1.9% of AUD criterion count in EUR and 1.3% in AFR. A combination of education, substance use in the household before age 13, annual household income, and male sex explained 73% of the variance in AUD criterion count in AFR and 59% in EUR sample. Thus, in both populations, environmental factors explained most of the explicable variance in AUD criterion count, but PRS was also a statistically significant predictor. Data pertaining to other SUDs will be presented as well.
Dr Michal Graczyk will explore how genetic vulnerability to addiction manifests in real-world healthcare behaviours, drawing on data from over 377,000 UK Biobank participants.[3] He found that PRS for five SUDs (alcohol, tobacco, cocaine, opioids, cannabis)[4-6] associated with increased prescription medication use and healthcare contacts. In a phenome-wide study across 260 medications, individuals with higher SUD PRSs were more likely to use not only medications with abuse potential (e.g. opioids, gabapentinoids) but also medications not typically considered addictive but linked to medical morbidity (e.g. vasodilators). Substance-specific patterns emerged for a few classes, such as hypnotics in relation alcohol and opioid use disorder PRS. Mendelian randomization analyses further supported causal pathways from drug and tobacco use to regular use of non-opioid analgesics and antidepressants. These findings extend our understanding of addiction genetics by linking inherited risk to broader health system impacts.
Together, these presentations illustrate how genetic and environmental risk factors contribute not only to the development of psychiatric and substance use disorders, but also to broader patterns of healthcare behaviours.