Although synthetic associations explaining common GWAS signals for complex polygenic traits are certainly plausible and can occur under specific circumstances (e.g. NOD2 in CD), results from studies thus far suggest that these scenarios are actually a rarity. The idea that MRVs at a particular locus may be associated with complex traits of interest has been around for over a decade. We are now starting to accrue a growing body of empirical evidence in support of this hypothesis. The field of complex trait genetics has over the last few months engaged in discussions on the controversial topic of synthetic associations, but it transpires that there is little evidence to support this as a widespread scenario.
