Limitations include that the differences in ascertainment and phenotypic heterogeneity across cohorts might bias the results. Despite the high genetic correlation between AUD and AUDIT–P, they are not identical traits, which introduces heterogeneity. Also, differences in ascertainment among the cohorts may have introduced biases; for example, the QIMR Berghofer Australian Genetics of Depression Study (AGDS) cohort has high major depression comorbidity, and the Australian Genetics of Bipolar Disorder Study (GBP) cohort has high bipolar disorder comorbidity. Heterogeneity would, however, have been more likely to limit discovery than to create false positives. Additionally, although we tried to include all available samples for problematic drinking in multiple ancestries, the sample sizes in the non-EUR ancestries were still small for gene discovery and downstream analyses. The collection of data from individuals of diverse genetic ancestries is a critical next step in this field. With more multi-ancestral biobanks and large consortia becoming available, including future releases of data from MVP, the Global Biobank Meta-analysis Initiative57 and the All of Us Research Program58, we anticipate that the gap between findings in EUR and other populations
