Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute for Medical Research, Sydney, New South Wales 2010, Australia.
Sci Adv. 2019 Aug 14;5(8):eaaw3538. doi: 10.1126/sciadv.aaw3538. eCollection 2019 Aug.
Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large sample without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 quantitative traits in the UK Biobank and identified 75 significant vQTLs with < 2.0 × 10 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.
基因型-环境互作（GEI）是理解复杂性状变异的基本组成部分。然而，由于效应大小较小且难以监测环境波动，因此在人类中识别具有 GEI 效应的遗传变异仍然具有挑战性。在这里，我们证明，即使不测量环境因素，也可以从与大型样本中表型可变性相关的遗传变异中推断出 GEI。我们对欧洲血统的 348,501 名无亲缘关系个体进行了全基因组方差数量性状基因座（vQTL）分析，针对 UK Biobank 中的 13 个数量性状分析了约 560 万个变体，鉴定出了 75 个具有 < 2.0×10 的显著 vQTL，其中 9 个性状与肥胖有关。对五个环境因素进行的直接 GEI 分析表明，vQTL 强烈富集了 GEI 效应。我们的结果表明肥胖相关性状存在普遍的 GEI 效应，并证明了在没有环境数据的情况下检测 GEI。
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