Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bioinformatics. 2012 Jun 15;28(12):i121-6. doi: 10.1093/bioinformatics/bts229.
Complex diseases, such as Type 2 Diabetes Mellitus (T2D), result from the interplay of both environmental and genetic factors. However, most studies investigate either the genetics or the environment and there are a few that study their possible interaction in context of disease. One key challenge in documenting interactions between genes and environment includes choosing which of each to test jointly. Here, we attempt to address this challenge through a data-driven integration of epidemiological and toxicological studies. Specifically, we derive lists of candidate interacting genetic and environmental factors by integrating findings from genome-wide and environment-wide association studies. Next, we search for evidence of toxicological relationships between these genetic and environmental factors that may have an etiological role in the disease. We illustrate our method by selecting candidate interacting factors for T2D.
复杂疾病,如 2 型糖尿病(T2D),是由环境和遗传因素相互作用的结果。然而,大多数研究要么调查遗传因素,要么调查环境因素,只有少数研究在疾病背景下研究它们可能的相互作用。在记录基因与环境之间相互作用时,一个关键挑战包括选择要联合测试的基因和环境的哪些部分。在这里,我们通过对流行病学和毒理学研究的综合来解决这个挑战。具体来说,我们通过整合全基因组和全环境关联研究的结果,得出候选相互作用的遗传和环境因素列表。接下来,我们搜索这些遗传和环境因素之间是否存在毒理学关系,这些关系可能在疾病中具有病因作用。我们通过选择 T2D 的候选相互作用因素来说明我们的方法。