Optima Partners, Edinburgh, EH2 4HQ, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Nat Commun. 2024 Aug 26;15(1):7346. doi: 10.1038/s41467-024-51744-5.
Understanding how gene-environment interactions (GEIs) influence the circulating proteome could aid in biomarker discovery and validation. The presence of GEIs can be inferred from single nucleotide polymorphisms that associate with phenotypic variability - termed variance quantitative trait loci (vQTLs). Here, vQTL association studies are performed on plasma levels of 1463 proteins in 52,363 UK Biobank participants. A set of 677 independent vQTLs are identified across 568 proteins. They include 67 variants that lack conventional additive main effects on protein levels. Over 1100 GEIs are identified between 101 proteins and 153 environmental exposures. GEI analyses uncover possible mechanisms that explain why 13/67 vQTL-only sites lack corresponding main effects. Additional analyses also highlight how age, sex, epistatic interactions and statistical artefacts may underscore associations between genetic variation and variance heterogeneity. This study establishes the most comprehensive database yet of vQTLs and GEIs for the human proteome.
了解基因-环境相互作用（GEIs）如何影响循环蛋白质组有助于生物标志物的发现和验证。可以从与表型变异性相关的单核苷酸多态性（称为方差数量性状基因座（vQTLs））推断出 GEIs 的存在。在这里，对来自 52363 名英国生物库参与者的 1463 种蛋白质的血浆水平进行了 vQTL 关联研究。在 568 种蛋白质中鉴定出了 677 个独立的 vQTL。其中包括 67 个缺乏对蛋白质水平常规加性主效应的变体。在 101 种蛋白质和 153 种环境暴露之间鉴定出了 1100 多个 GEI。GEI 分析揭示了可能的机制，解释了为什么 13/67 的仅 vQTL 位点缺乏相应的主效应。额外的分析还强调了年龄、性别、上位性相互作用和统计假象如何可能强调遗传变异与方差异质性之间的关联。这项研究建立了迄今为止最全面的人类蛋白质组 vQTL 和 GEI 数据库。
