The utility of longitudinal, repeated AUDIT-C scores as a phenotype for harmful alcohol use may depend on the type of EHR data employed, the length of the observation period, and the statistical approach. In a prior publication, we demonstrated that a single AUDIT-C value did not have as strong a protective association with the ADH1B variants as did repeated longitudinal AUDIT-C measures incorporated into trajectories (8). This was true even when the highest AUDIT-C value was selected. In this study, our sample had an average of 7 annual AUDIT-C measurements. It provided evidence that a highly generalizable phenotype based on quantity-frequency data is valid. Because we age adjust the mean AUDIT-C, our finding could be directly reproduced in other samples with differing age distributions. Because the replication of genetic associations using independent data is an essential component of genetic discovery, having a simple, highly discriminating and generalizable phenotype is a major advance for such studies.
