Department of Sociology, University of Colorado Boulder, Boulder, CO, USA.
Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Sci Rep. 2021 Oct 13;11(1):20332. doi: 10.1038/s41598-021-98684-4.
We re-evaluate the findings of one of the most cited and disputed papers in gene-environment interaction (GxE) literature. In 2003, a paper was published in Science in which the authors demonstrated that the relationship between stress and depression is moderated by a polymorphism in the promoter region (5-HTTLPR) of the gene SLC6A4. Replication has been weak and led many to challenge the overall significance of GxE research. Here, we utilize data from Add Health, a large, nationally representative, and well-powered longitudinal study to re-examine the genetic determinants of stress sensitivity. We characterize environmental sensitivity using a genome-wide polygenic indicator rather than relying on one polymorphism in a single candidate gene. Our results provide support for the stress-diathesis perspective and validate the scientific contributions of the original paper.
我们重新评估了基因-环境相互作用（GxE）文献中最常被引用和争议最大的论文之一的结果。2003 年，一篇论文发表在《科学》杂志上，作者证明了基因 SLC6A4 启动子区域（5-HTTLPR）的多态性调节了压力和抑郁之间的关系。复制结果一直很弱，导致许多人质疑 GxE 研究的总体意义。在这里，我们利用 Add Health 的数据，这是一项大型的、具有全国代表性的、功能强大的纵向研究，重新研究压力敏感性的遗传决定因素。我们使用全基因组多基因指标来描述环境敏感性，而不是依赖于单个候选基因中的一个多态性。我们的研究结果支持压力素质观点，并验证了原始论文的科学贡献。
