Gene–environment interactions in human health

IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY Nature Reviews Genetics Pub Date : 2024-05-28 DOI:10.1038/s41576-024-00731-z
Esther Herrera-Luis, Kelly Benke, Heather Volk, Christine Ladd-Acosta, Genevieve L. Wojcik
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Abstract

Gene–environment interactions (G × E), the interplay of genetic variation with environmental factors, have a pivotal impact on human complex traits and diseases. Statistically, G × E can be assessed by determining the deviation from expectation of predictive models based solely on the phenotypic effects of genetics or environmental exposures. Despite the unprecedented, widespread and diverse use of G × E analytical frameworks, heterogeneity in their application and reporting hinders their applicability in public health. In this Review, we discuss study design considerations as well as G × E analytical frameworks to assess polygenic liability dependent on the environment, to identify specific genetic variants exhibiting G × E, and to characterize environmental context for these dynamics. We conclude with recommendations to address the most common challenges and pitfalls in the conceptualization, methodology and reporting of G × E studies, as well as future directions. Despite their impact on human complex traits and diseases, gene–environment interactions (G × E) remain challenging to assess statistically. The authors review considerations for the conceptualization, methodology, interpretation and reporting of G × E studies, and provide recommendations on how to avoid common pitfalls.

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人类健康中基因与环境的相互作用。
基因与环境的相互作用(G×E),即遗传变异与环境因素的相互作用,对人类复杂的性状和疾病有着举足轻重的影响。从统计学角度看,G × E 可通过确定预测模型的预期偏差来评估,而预测模型的预期偏差则完全基于遗传或环境暴露的表型效应。尽管 G × E 分析框架得到了前所未有的广泛和多样化应用,但其应用和报告的异质性阻碍了其在公共卫生领域的适用性。在本综述中,我们将讨论研究设计的注意事项以及 G × E 分析框架,以评估依赖于环境的多基因责任,确定表现出 G × E 的特定遗传变异,并描述这些动态的环境背景。最后,我们针对 G × E 研究的概念化、方法学和报告中最常见的挑战和误区提出了建议以及未来的发展方向。
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来源期刊
Nature Reviews Genetics
Nature Reviews Genetics 生物-遗传学
CiteScore
57.40
自引率
0.50%
发文量
113
审稿时长
6-12 weeks
期刊介绍: At Nature Reviews Genetics, our goal is to be the leading source of reviews and commentaries for the scientific communities we serve. We are dedicated to publishing authoritative articles that are easily accessible to our readers. We believe in enhancing our articles with clear and understandable figures, tables, and other display items. Our aim is to provide an unparalleled service to authors, referees, and readers, and we are committed to maximizing the usefulness and impact of each article we publish. Within our journal, we publish a range of content including Research Highlights, Comments, Reviews, and Perspectives that are relevant to geneticists and genomicists. With our broad scope, we ensure that the articles we publish reach the widest possible audience. As part of the Nature Reviews portfolio of journals, we strive to uphold the high standards and reputation associated with this esteemed collection of publications.
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