Interactions between polygenic scores and environments: Methodological and conceptual challenges

Interest in the study of gene-environment interaction has recently grown due to the sudden availability of molecular genetic data-in particular, polygenic scores-in many long-running longitudinal studies. Identifying and estimating statistical interactions comes with several analytic and inferential challenges; these challenges are heightened when used to integrate observational genomic and social science data. We articulate some of these key challenges, provide new perspectives on the study of gene-environment interactions, and end by offering some practical guidance for conducting research in this area. Given the sudden availability of well-powered polygenic scores, we anticipate a substantial increase in research testing for interaction between such scores and environments. The issues we discuss, if not properly addressed, may impact the enduring scientific value of gene-environment interaction studies.