Department of Human Genetics, University of California, Los Angeles, CA, 90095, USA.
Am J Hum Genet. 2010 Mar 12;86(3):399-410. doi: 10.1016/j.ajhg.2010.02.002. Epub 2010 Feb 18.
Gene by environment (GxE) interactions are clearly important in many human diseases, but they have proven to be difficult to study on a molecular level. We report genetic analysis of thousands of transcript abundance traits in human primary endothelial cell (EC) lines in response to proinflammatory oxidized phospholipids implicated in cardiovascular disease. Of the 59 most regulated transcripts, approximately one-third showed evidence of GxE interactions. The interactions resulted primarily from effects of distal-, trans-acting loci, but a striking example of a local-GxE interaction was also observed for FGD6. Some of the distal interactions were validated by siRNA knockdown experiments, including a locus involved in the regulation of multiple transcripts involved in the ER stress pathway. Our findings add to the understanding of the overall architecture of complex human traits and are consistent with the possibility that GxE interactions are responsible, in part, for the failure of association studies to more fully explain common disease variation.
基因与环境（GxE）相互作用在许多人类疾病中显然很重要，但在分子水平上研究它们已被证明具有挑战性。我们报告了对涉及心血管疾病的促炎氧化磷脂的人类原代内皮细胞（EC）系中数千个转录丰度性状的遗传分析。在 59 个调节最明显的转录本中，约有三分之一表现出 GxE 相互作用的证据。这些相互作用主要来自远端、反式作用基因座的影响，但也观察到了 FGD6 中一个明显的局部 GxE 相互作用的例子。一些远端相互作用通过 siRNA 敲低实验得到了验证，其中包括一个调节涉及内质网应激途径的多个转录本的基因座。我们的发现增加了对复杂人类特征整体结构的理解，并与 GxE 相互作用部分负责关联研究未能更充分解释常见疾病变异的可能性一致。
