人类的健康状况受到基因（G）和环境（E）的共同决定。这一点在同一环境因素下暴露的个体群体中表现出不同反应的情况下得到了清晰的证明。对于基因-环境相互作用（GxE）的量化测量尚未开发出来，在某些情况下，甚至都没有对该概念达成明确共识；例如，癌症主要是由“厄运”还是“不良生活方式”所致仍存在争议。在本文中，我们提供了一系列GxE相互作用作为病因的例证。我们强调表观遗传调控可以作为分子基础的一个共同联系方面。我们的论点聚焦于GxE记录在细胞表观基因组中，这可能是解析这些多维纠缠的调控层的关键。开发一种解读这一表观遗传信息的关键将为疾病风险提供量化测量。类似于用于估计生物年龄的表观时钟，我们大胆地提出了一个理论概念，即“表观评分器”，用于估计疾病风险。© 2023 The Authors. Published under the terms of the CC BY 4.0 license.

Human health is determined both by genetics (G) and environment (E). This is clearly illustrated in groups of individuals who are exposed to the same environmental factor showing differential responses. A quantitative measure of the gene-environment interactions (GxE) effects has not been developed and in some instances, a clear consensus on the concept has not even been reached; for example, whether cancer is predominantly emerging from "bad luck" or "bad lifestyle" is still debated. In this article, we provide a panel of examples of GxE interaction as drivers of pathogenesis. We highlight how epigenetic regulations can represent a common connecting aspect of the molecular bases. Our argument converges on the concept that the GxE is recorded in the cellular epigenome, which might represent the key to deconvolute these multidimensional intricated layers of regulation. Developing a key to decode this epigenetic information would provide quantitative measures of disease risk. Analogously to the epigenetic clock introduced to estimate biological age, we provocatively propose the theoretical concept of an "epigenetic score-meter" to estimate disease risk.© 2023 The Authors. Published under the terms of the CC BY 4.0 license.