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Polygenic Scores for Plasticity: A New Tool for Studying Gene-Environment Interplay

By Rebecca Johnson, Ramina Sotoudeh, Dalton Conley

Posted 31 Aug 2020
bioRxiv DOI: 10.1101/2020.08.30.274530

Outcomes of interest to demographers—fertility; health; education—are the product of both an individual’s genetic makeup and his or her social environment. Yet Gene × Environment research (GxE) currently deploys a limited toolkit on the genetic side to study gene-environment interplay: polygenic scores (PGS, or what we call mPGS) that reflect the influence of genetics on levels of an outcome. The purpose of the present paper is to develop a genetic summary measure better suited for GxE research. We develop what we call variance polygenic scores (vPGS), or polygenic scores that reflect genetic contributions to plasticity in outcomes. The first part of the analysis uses the UK Biobank (N ∼ 326,000 in the training set) and the Health and Retirement Study (HRS) (N = 10,524) to compare four approaches for constructing polygenic scores for plasticity. The results show that two widely-used methods for discovering which genetic variants affect outcome variability fail to serve as distinctive new tools for GxE. Then, using the polygenic scores that do capture distinctive genetic contributions to plasticity, we analyze heterogeneous effects of a UK education reform on health and educational attainment. The results show the properties of a new tool useful for population scientists studying the interplay of nature and nurture and for population-based studies that are releasing polygenic scores to applied researchers. ### Competing Interest Statement The authors have declared no competing interest.

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