Finally, another possibility is gene-environment interactions (e.g. as proposed for rs1801282 and low physical activity [27]) with differential non-genetic environmental exposures across different populations. Moreover, genuine genetic heterogeneity in effect sizes across different ethnic backgrounds and population-specific gene-gene epistatic effects are sometimes postulated. However, interaction effects (effect modification) may require huge studies to confirm [28], much larger than even the very large consortia that have been put together in the genetics of type 2 diabetes.
