Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Sci Rep. 2018 Jan 8;8(1):17. doi: 10.1038/s41598-017-18585-3.
While both genes and environment contribute to phenotype, deciphering environmental contributions to phenotype is a challenge. Furthermore, elucidating how different phenotypes may share similar environmental etiologies also is challenging. One way to identify environmental influences is through a discordant monozygotic (MZ) twin study design. Here, we assessed differential gene expression in MZ discordant twin pairs (affected vs. non-affected) for seven phenotypes, including chronic fatigue syndrome, obesity, ulcerative colitis, major depressive disorder, intermittent allergic rhinitis, physical activity, and intelligence quotient, comparing the spectrum of genes differentially expressed across seven phenotypes individually. Second, we performed meta-analysis for each gene to identify commonalities and differences in gene expression signatures between the seven phenotypes. In our integrative analyses, we found that there may be a common gene expression signature (with small effect sizes) across the phenotypes; however, differences between phenotypes with respect to differentially expressed genes were more prominently featured. Therefore, defining common environmentally induced pathways in phenotypes remains elusive. We make our work accessible by providing a new database (DiscTwinExprDB: http://apps.chiragjpgroup.org/disctwinexprdb/ ) for investigators to study non-genotypic influence on gene expression.
虽然基因和环境都对表型有贡献，但要破解环境对表型的贡献是一个挑战。此外，阐明不同的表型如何可能具有相似的环境病因也具有挑战性。一种识别环境影响的方法是通过不一致的同卵（MZ）双胞胎研究设计。在这里，我们评估了 MZ 不一致双胞胎对（受影响与未受影响）的七种表型（包括慢性疲劳综合征、肥胖、溃疡性结肠炎、重度抑郁症、间歇性过敏性鼻炎、体力活动和智商）的差异基因表达，比较了七种表型各自的差异表达基因谱。其次，我们对每个基因进行了荟萃分析，以确定七种表型之间基因表达特征的共性和差异。在我们的综合分析中，我们发现可能存在一个跨越表型的共同基因表达特征（具有小的效应大小）；然而，表型之间在差异表达基因方面的差异更为显著。因此，定义表型中常见的环境诱导途径仍然难以捉摸。我们提供了一个新的数据库（DiscTwinExprDB：http://apps.chiragjpgroup.org/disctwinexprdb/），供研究人员研究非基因型对基因表达的影响，使我们的工作易于访问。
