Genetic Studies in Indigenous Populations
There have also been a few research efforts to elucidate the genetic variants predisposing Native Americans and Aboriginal communities to ion channelopathies. Historically, there has been a paucity of data on Indigenous populations in large genomic datasets such as the Genome Aggregation Database.8 Furthermore, it is apparent that Indigenous populations have not yet experienced the benefits of technological advancements that aid genomic research and the diagnosis of rare diseases, including CVD.7 These disparities are even more pronounced in the research of ion channelopathies in these populations despite ongoing efforts to address these gaps. Swayne et al. identified a novel ANK2 variant in multigenerational families, the carriers of which showed LQTS and exhibited signs of structural heart disease, including one with cardiomyopathy resulting in SCD.37 Two other studies highlighted the same missense mutation in the KCNQ1 (V205M) associated with hereditary LQTS in First Nations subgroups in Northern British Columbia.38, 39 The V205M variant showed variable effect in clinical expression, as 30% of the mutation carriers still had a corrected QT interval under 440ms, showing the heterogeneous nature of hereditary LQTS, especially in this specific demographic. While these studies add significantly to the growing knowledge of ion channelopathies in Native American and Indigenous populations, further research is needed to adequately characterize these arrhythmogenic conditions from genetic factors to the overall clinical management in these underserved populations.