A Community-Based Approach for ALDH2 Genetic Testing in East Asian Americans

Alcohol flushing syndrome affects an estimated >500 million individuals worldwide and is strongly associated with functional variants in alcohol metabolism genes, particularly ALDH2 (e.g., ALDH2*2) and ADH1B (e.g., ADH1B*2). ALDH2*2 reduces aldehyde dehydrogenase activity, contributing to acetaldehyde accumulation and is associated with increased risk for alcohol-related morbidity, including certain cancers and cardiometabolic outcomes. Despite the public health relevance, ALDH2/ADH1B implementation in clinical care remains limited, and evidence-based strategies are needed to support equitable and ethical adoption, especially for populations underrepresented in genomics research. This study will engage the East Asian American community to evaluate implementation strategies for ALDH2*2 and ADH1B*2 genetic testing and education in clinical settings and to examine the behavioral impact of returning genetic risk information. Using a pragmatic, randomized comparative effectiveness pilot design, East Asian American adults who self-report alcohol flushing and/or a family history of flushing will be randomized to either: (1) education plus ALDH2*2/ADH1B*2 genetic testing with genotype-informed result disclosure, or (2) education alone. Primary outcomes are feasibility and acceptability of the testing-and-education approach; secondary outcomes include changes in modifiable health behaviors (e.g., alcohol-related decision-making) following education with or without genetic result return. Findings will inform scalable implementation pathways and contribute to equitable integration of genomic testing into routine care for populations experiencing healthcare disparities.