Dickson et al. [4] used simulation to determine if associations detected in GWAS could reflect synthetic associations of single or multiple rare causal variants. Their abstract states, “We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies.” Their results have been interpreted by the scientific community to imply that this mechanism could apply to an important proportion of associations detected in GWAS. Benchmarking the importance of synthetic associations with rare causal variants is relevant for determining the direction of future research.
