ArticleAddiction (Abingdon, England)2025
Genetic risk for alcohol use disorder in relation to individual symptom criteria: Do polygenic indices provide unique information for understanding severity and heterogeneity?
Article in Addiction (Abingdon, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Assessing measurement bias in substance use disorder criteria associated with childhood adversity and genetic liability.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2026Article
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Abstract
BACKGROUND AND
aimsPrevious studies have suggested that Alcohol Use Disorder (AUD) might result from separable genetic influences with symptoms reflecting differing degrees of genetic risk related to distinct risk mechanisms. The present study aimed to examine the genetic risk for individual AUD symptom criteria using a polygenic risk score (PRS) approach to assess the relative severity of each symptom and test for a multidimensional genetic structure of AUD.
designThis retrospective study examined the correlation between genetic severity (i.e. PRS) and Item Response Theory (IRT) severity indices for each AUD symptom. Multiple Indicators Multiple Causes (MIMIC) models were employed to examine the effect of the PRS on individual AUD symptoms after accounting for overall AUD severity. SETTING AND
participantsThe study made use of summary-level data produced in Finland, United Kingdom and the United States of America as well as individual-level data from 1639 participants of the University of California - San Francisco Family Alcoholism Study. MEASUREMENTS: Phenotypic measures included the 11 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) AUD symptom criteria assessed using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism. AUD, Problematic Alcohol Use (PAU) and alcohol consumption [i.e. drinks per week (DPW)] PRSs were created using summary statistics obtained from published genome-wide association studies (GWAS).
findingsPhenotypic and genotypic severities of AUD symptoms were statistically significantly correlated for the PAU PRS and AUD PRS (r range = 0.77-0.89), but not for the DPW PRS (r = 0.45). MIMIC models indicated that the PRSs statistically significantly predicted the AUD factor. Regression paths testing the direct effects of the PRSs on individual AUD symptoms, independent of the latent AUD factor, were statistically nonsignificant.
conclusionsPolygenic risk scores derived from genome-wide association studies (GWAS) of alcohol use disorder (AUD) appear to influence AUD symptom expression through a single genetic factor that is highly correlated with the relative severity of individual symptoms measured at the phenotypic level. Item-level GWAS of AUD symptoms are needed to further parse heterogeneous symptom expression and allow for more nuanced tests of these conclusions.
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