Examining the Etiological Specificity of Genetic Risk for Alcohol Use Disorder and Alcohol Consumption through Symptom-Level Mediation Analyses

In the UCSF Family Alcoholism Study, an AUD polygenic score’s links to individual AUD symptoms are fully mediated by maximum habitual drinks (N = 1,611) and partially by neuroticism for nearly all symptoms.

• Why it matters: It is unclear whether AUD polygenic scores reflect genetic liability specific to alcohol use or also capture broader transdiagnostic traits that shape how AUD symptoms present.
• What they did: Separate mediation models tested maximum habitual drinks and MMPI-2 PSY-5 scales as mediators of AUD and alcohol consumption PGS associations with individual AUD symptoms, using Bonferroni correction (p < .0045).
• The result: Alcohol consumption PGS effects on AUD symptoms are fully mediated by maximum habitual drinks alone, with no mediation via any personality psychopathology measure, implying predominantly consumption-linked genetic influence.

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