McCourt School of Public Policy, Georgetown University, Washington, DC, USA.
Nuffield College, University of Oxford, Oxford, UK.
Demography. 2022 Jun 1;59(3):1045-1070. doi: 10.1215/00703370-9957418.
Fertility, health, education, and other outcomes of interest to demographers are the product of an individual's genetic makeup and their social environment. Yet, gene × environment (G×E) research deploys a limited toolkit on the genetic side to study the gene-environment interplay, relying on polygenic scores (PGSs) that reflect the influence of genetics on levels of an outcome. In this article, we develop a genetic summary measure better suited for G×E research: variance polygenic scores (vPGSs), which are PGSs that reflect genetic contributions to plasticity in outcomes. First, we use the UK Biobank (N ∼ 408,000 in the analytic sample) and the Health and Retirement Study (N ∼ 5,700 in the analytic sample) to compare four approaches to constructing PGSs for plasticity. The results show that widely used methods for discovering which genetic variants affect outcome variability fail to serve as distinctive new tools for G×E. Second, using the PGSs 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 useful new tool for population scientists studying the interplay of nature and nurture and for population-based studies that are releasing PGSs to applied researchers.
生育力、健康、教育和其他人口统计学家感兴趣的结果是个人的遗传构成和社会环境的产物。然而，基因与环境（G×E）研究在遗传方面仅使用有限的工具包来研究基因-环境相互作用，依赖于多基因评分（PGS），它反映了遗传对结果水平的影响。在本文中，我们开发了一种更适合 G×E 研究的遗传综合衡量标准：方差多基因评分（vPGS），它是反映遗传对结果可塑性贡献的 PGS。首先，我们使用英国生物库（分析样本中约 408000 人）和健康与退休研究（分析样本中约 5700 人）比较了构建用于可塑性的 PGS 的四种方法。结果表明，广泛用于发现哪些遗传变异会影响结果变异性的方法并不能作为 G×E 的独特新工具。其次，使用确实能捕捉到对可塑性有独特遗传贡献的 PGS，我们分析了英国教育改革对健康和教育程度的异质影响。结果表明，这是一种用于研究自然与教养相互作用的人口统计学家和向应用研究人员发布 PGS 的基于人群的研究的有用新工具的特性。
