夫妻转录相似性揭示了共同环境和生活方式通过修饰的胞嘧啶对基因调控的影响
Transcriptional Similarity in Couples Reveals the Impact of Shared Environment and Lifestyle on Gene Regulation through Modified Cytosines
摘要：
基因表达是一种复杂的数量性状，受遗传和非遗传调节因子（包括环境因素）的影响。评估环境对基因表达调控的贡献，并确定哪些基因更可能受到环境因素的影响，对于理解人类复杂的性状是很重要的。我们假设，通过夫妻生活在一起，可能存在共同调节的基因，这些基因可能反映了共同的生活环境（例如，饮食、室内空气污染物、行为生活方式）。来自国际人类基因组单体型图计划的非洲血统无关夫妇（YRI，来自尼日利亚伊巴丹的约鲁巴人）的淋巴母细胞样细胞系（LCL）为我们通过比较丈夫和妻子之间的基因表达水平来表征夫妇中的基因表达模式提供了独特的模型。引人注目的是，在5%的错误发现率（FDR）下，发现778个基因在夫妇中的变异比随机配对的个体小得多。由于假设随机交配社会，一般人群中无关家庭成员之间的遗传变异预计是相同的，因此非遗传因素（例如，表观遗传系统）更可能是夫妇中观察到的转录相似性的介导者。因此，我们评估了修饰的胞嘧啶对那些在夫妇中显示转录相似性的基因的贡献，以及这些CpG位点与其他基因调控元件，如转录因子结合位点（TFBS）的关系。我们的研究结果表明，夫妇的转录相似性可能反映了共享的共同环境，部分通过胞嘧啶修饰介导。
英文摘要：
Gene expression is a complex and quantitative trait that is influenced by both genetic and non-genetic regulators including environmental factors. Evaluating the contribution of environment to gene expression regulation and identifying which genes are more likely to be influenced by environmental factors are important for understanding human complex traits. We hypothesize that by living together as couples, there can be commonly co-regulated genes that may reflect the shared living environment (e.g., diet, indoor air pollutants, behavioral lifestyle). The lymphoblastoid cell lines (LCLs) derived from unrelated couples of African ancestry (YRI, Yoruba people from Ibadan, Nigeria) from the International HapMap Project provided a unique model for us to characterize gene expression pattern in couples by comparing gene expression levels between husbands and wives. Strikingly, 778 genes were found to show much smaller variances in couples than random pairs of individuals at a false discovery rate (FDR) of 5%. Since genetic variation between unrelated family members in a general population is expected to be the same assuming a random-mating society, non-genetic factors (e.g., epigenetic systems) are more likely to be the mediators for the observed transcriptional similarity in couples. We thus evaluated the contribution of modified cytosines to those genes showing transcriptional similarity in couples as well as the relationships these CpG sites with other gene regulatory elements, such as transcription factor binding sites (TFBS). Our findings suggested that transcriptional similarity in couples likely reflected shared common environment partially mediated through cytosine modifications.
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