Multi-Ancestry Rare and Low-Frequency Variant Analysis Reveals Novel and Convergent Biological Pathways for Cannabis Use Disorder

Rare and low-frequency variant analyses across American Indians, Mexican Americans, and European Americans identify convergent and ancestry-specific biological pathways linked to Cannabis Use Disorder severity, including arylsulfatases activation and heparan sulfate degradation.

• Why it matters: Genetic studies of Cannabis Use Disorder have largely emphasized European descent, leaving disparities across U.S ethnic groups insufficiently explained and limiting insight into severity-linked biology.
• What they did: Using a validated composite of 20 cannabis-related life events to quantify CUD severity, the study analyzed rare and low-frequency functional variants (minor allele frequency < 5%) across three ancestry groups.
• The result: In Mexican Americans, the arylsulfatases activation pathway was significantly associated with CUD severity and supported in American Indians, while European Americans showed a significant negative association for the heparan sulfate degradation pathway; immune p38-gamma/delta MAPK signaling was supported across cohorts.

AI summary of the abstract · may contain errors · not medical advice · read the paper.