Mulligan Connie J, Quinn Edward B, Hamadmad Dima, Dutton Christopher L, Nevell Lisa, Binder Alexandra M, Panter-Brick Catherine, Dajani Rana
Department of Anthropology, University of Florida, Gainesville, FL, USA.
Genetics Institute, University of Florida, Gainesville, FL, USA.
Sci Rep. 2025 Feb 27;15(1):5945. doi: 10.1038/s41598-025-89818-z.
Maternal trauma influences infant and adult health outcomes and may impact future generations through epigenetic modifications such as DNA methylation (DNAm). Research in humans on the intergenerational epigenetic transmission of trauma effects is limited. In this study, we assessed DNAm signatures of war-related violence by comparing germline, prenatal, and direct exposures to violence across three generations of Syrian refugees. We compared families in which a pregnant grandmother versus a pregnant mother was exposed to violence and included a control group with no exposure to war. We collected buccal swab samples and survey data from mothers and 1-2 children in each of 48 families (n = 131 participants). Based on an epigenome-wide association study (EWAS), we identified differentially methylated regions (DMPs): 14 were associated with germline and 21 with direct exposure to violence. Most DMPs showed the same directionality in DNAm change across germline, prenatal, and direct exposures, suggesting a common epigenetic response to violence. Additionally, we identified epigenetic age acceleration in association with prenatal exposure to violence in children, highlighting the critical period of in utero development. This is the first report of an intergenerational epigenetic signature of violence, which has important implications for understanding the inheritance of trauma.
母亲遭受创伤会影响婴儿和成人的健康结果，并可能通过DNA甲基化（DNAm）等表观遗传修饰影响后代。关于创伤效应的跨代表观遗传传递的人体研究有限。在本研究中，我们通过比较三代叙利亚难民的种系、产前和直接暴力暴露情况，评估了与战争相关暴力的DNAm特征。我们比较了怀孕祖母与怀孕母亲遭受暴力的家庭，并纳入了未经历战争的对照组。我们从48个家庭中的母亲和1-2名儿童那里收集了口腔拭子样本和调查数据（n = 131名参与者）。基于全基因组关联研究（EWAS），我们确定了差异甲基化区域（DMP）：14个与种系相关，21个与直接暴力暴露相关。大多数DMP在种系、产前和直接暴露的DNAm变化中显示出相同的方向性，这表明对暴力存在共同的表观遗传反应。此外，我们发现儿童产前暴露于暴力与表观遗传年龄加速有关，突出了子宫内发育的关键时期。这是关于暴力跨代表观遗传特征的首次报告，对理解创伤的遗传具有重要意义。
