美国芝加哥大学Luis B. Barreiro等研究人员合作发现，表观遗传变异影响流感感染转录反应的个体差异。该项研究成果于2024年2月29日在线发表在《自然—遗传学》杂志上。

研究人员对来自欧洲和非洲血统的原代巨噬细胞在感染甲型流感病毒前后进行了深入的遗传、表观遗传和转录谱分析。研究表明，基线表观遗传学特征可有力地预测不同个体对甲型流感病毒的转录反应。定量性状位点（QTL）图显示了基因调控的高度协调遗传效应，许多顺式作用的遗传变异同时影响基因表达和多种表观遗传标记。这些数据揭示，与祖先相关的表观遗传景观差异可以由基因控制，甚至比基因表达更重要。

最后，在与免疫疾病基因座共定位的QTL变异中，只有7%是基因表达QTL，而其余的基因变异则影响表观遗传标记，这强调了在以疾病为重点的研究中考虑基因表达之外的分子表型的重要性。

研究人员表示，人类对相同挑战的免疫反应显示出显著的个体差异。然而，人们对导致这种差异的遗传和表观遗传因素的了解仍然有限。

附：英文原文

Title: Epigenetic variation impacts individual differences in the transcriptional response to influenza infection

Author: Aracena, Katherine A., Lin, Yen-Lung, Luo, Kaixuan, Pacis, Alain, Gona, Saideep, Mu, Zepeng, Yotova, Vania, Sindeaux, Renata, Pramatarova, Albena, Simon, Marie-Michelle, Chen, Xun, Groza, Cristian, Lougheed, David, Gregoire, Romain, Brownlee, David, Boye, Carly, Pique-Regi, Roger, Li, Yang, He, Xin, Bujold, David, Pastinen, Tomi, Bourque, Guillaume, Barreiro, Luis B.

Issue&Volume: 2024-02-29

Abstract: Humans display remarkable interindividual variation in their immune response to identical challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we performed in-depth genetic, epigenetic and transcriptional profiling on primary macrophages derived from individuals of European and African ancestry before and after infection with influenza A virus. We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to influenza A virus across individuals. Quantitative trait locus (QTL) mapping revealed highly coordinated genetic effects on gene regulation, with many cis-acting genetic variants impacting concomitantly gene expression and multiple epigenetic marks. These data reveal that ancestry-associated differences in the epigenetic landscape can be genetically controlled, even more than gene expression. Lastly, among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, while the remaining genetic variants impact epigenetic marks, stressing the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.

DOI: 10.1038/s41588-024-01668-z

Source: https://www.nature.com/articles/s41588-024-01668-z