Making a decision: Weighing the scientific and social concerns in using Ancestry Informative Markers (AIMs) in genetic association studies

Genome-wide association studies have identified a large number of genetic associations in various common diseases. Emphasis is now shifting to the replication of these associations. In this context, the ability to account for systematic differences in the genetic background of study populations (population stratification) remains a practical concern for genetic epidemiology practice. While ancestry estimation using ancestry informative markers (AIMs) has become a common approach to address population stratification, the impact and justification of this practice remains obscure. To better understand the impact of using ancestry estimation to address population stratification, a content analysis of 58 articles that use AIMs to address population stratification was conducted. Overall, articles provided limited description of how AIMs were selected and used. Justification for using AIMs took the form of general concern for population stratification and presumed admixture of study populations. Most significant, ancestry estimation had little to no impact on the majority of association results. Given the potential social harms attributed to ancestry estimation and (according to this analysis) the limited impact of ancestry estimation on study results, scientists should avoid using AIMs in association studies to address population stratification unless justified by an impact on study results. Attention to the effects of population structure is, nevertheless, still warranted. Preferred alternatives are either to report association results without ancestry information (when ancestry estimation has no net effect) or to use randomly-selected markers instead of AIMs.