Garao Rico Andre Luis, Palmiero Nicole, Ritchie Marylyn D, Hall Molly A
Department of Genetics, University of Pennsylvania, 3700 Hamilton Walk Philadelphia, PA 19104, USA,
Pac Symp Biocomput. 2025;30:535-550. doi: 10.1142/9789819807024_0038.
Gene-environment interaction (GxE) studies provide insights into the interplay between genetics and the environment but often overlook multiple environmental factors' synergistic effects. This study encompasses the use of environment by environment interaction (ExE) studies to explore interactions among environmental factors affecting lipid phenotypes (e.g., HDL, LDL, and total cholesterol, and triglycerides), which are crucial for disease risk assessment. We developed a novel curated knowledge base, GE.db, integrating genomic and exposomic interactions. In this study, we filtered NHANES exposure variables (available 1999-2018) to identify significant ExE using GE.db. From 101,316 participants and 77 exposures, we identified 263 statistically significant interactions (FDR p < 0.1) in discovery and replication datasets, with 21 interactions significant for HDL-C (Bonferroni p < 0.05). Notable interactions included docosapentaenoic acid (22:5n-3) (DPA) - arachidic acid (20:0), stearic acid (18:0) - arachidic acid (20:0), and blood 2,5-dimethyfuran - blood benzene associated with HDL-C levels. These findings underscore GE.db's role in enhancing -omics research efficiency and highlight the complex impact of environmental exposures on lipid metabolism, informing future health strategies.
基因-环境相互作用（GxE）研究有助于深入了解基因与环境之间的相互作用，但往往忽视了多种环境因素的协同效应。本研究采用环境间相互作用（ExE）研究方法，以探索影响脂质表型（如高密度脂蛋白、低密度脂蛋白、总胆固醇和甘油三酯）的环境因素之间的相互作用，这些脂质表型对疾病风险评估至关重要。我们开发了一个新的精选知识库GE.db，整合了基因组和暴露组相互作用。在本研究中，我们使用GE.db对美国国家健康与营养检查调查（NHANES，1999 - 2018年数据可用）的暴露变量进行筛选，以识别显著的ExE。在101316名参与者和77种暴露因素中，我们在发现和复制数据集中识别出263个具有统计学意义的相互作用（错误发现率p < 0.1），其中21个相互作用对高密度脂蛋白胆固醇（HDL-C）具有显著意义（Bonferroni校正p < 0.05）。值得注意的相互作用包括二十二碳五烯酸（22:5n-3）（DPA）-花生酸（20:0）、硬脂酸（18:0）-花生酸（20:0）以及血液中的2,5-二甲基呋喃-血液中的苯与HDL-C水平相关。这些发现强调了GE.db在提高组学研究效率方面的作用，并突出了环境暴露对脂质代谢的复杂影响，为未来的健康策略提供了参考。
