Abstract：
Social anxiety disorder (SAD) and panic disorder (PD) are prevalent anxiety disorders characterized by a complex interplay of genetic and environmental factors. Both disorders share overlapping features and often coexist, despite displaying distinct characteristics. Childhood life adversity, overall stressful life events, and genetic factors contribute to the development of these disorders. DNA methylation, an epigenetic modification, has been implicated in the pathogenesis of these diseases. In this study, we investigated whether whole-genome DNA methylation risk scores (MRSs) for SAD risk, severity of social anxiety, childhood life adversity, PD risk, and overall stressful life events were associated with SAD or PD case‒control status. Preliminary epigenome-wide association studies (EWASs) for SAD risk, severity of social anxiety, and childhood life adversity were conducted in 66 SAD individuals and 77 healthy controls (HCs). Similarly, EWASs for PD risk and overall stressful life events were performed in 182 PD individuals and 81 HCs. MRSs were calculated from these EWASs. MRSs derived from the EWASs of SAD risk and severity of social anxiety were greater in PD patients than in HCs. Additionally, MRSs derived from the EWASs of overall stressful life events, particularly in PD individuals, were lower in SAD individuals than in HCs. In contrast, MRSs for childhood life adversity or PD risk were not significantly associated with PD or SAD case‒control status. These findings highlight the epigenetic features shared in both disorders and the distinctive epigenetic features related to social avoidance in SAD patients, helping to elucidate the epigenetic basis of these disorders.
摘要：
社交焦虑障碍（SAD）和恐慌症（PD）是普遍存在的焦虑障碍，其特征是遗传和环境因素的复杂相互作用。两种疾病都有重叠的特征，并且经常共存，尽管表现出明显的特征。童年生活的逆境，整体紧张的生活事件，遗传因素有助于这些疾病的发展。DNA甲基化，表观遗传修饰，与这些疾病的发病机理有关。在这项研究中,我们调查了SAD风险的全基因组DNA甲基化风险评分(MRS)社交焦虑的严重程度，童年生活逆境，PD风险，总体压力生活事件与SAD或PD病例对照状态相关。SAD风险的初步表观基因组关联研究(EWASs)，社交焦虑的严重程度，在66名SAD个体和77名健康对照（HCs）中进行了儿童生活逆境。同样，在182名PD个体和81名HCs中进行了PD风险和总体压力生活事件的EWAS。MRS是从这些EWAS计算的。PD患者的SAD风险EWASs和社交焦虑严重程度高于HCs。此外,MRS源自整体压力生活事件的EWAS，特别是在PD个体中，SAD个体低于HCs。相比之下,儿童生活逆境或PD风险的MRS与PD或SAD病例对照状态没有显着相关。这些发现强调了两种疾病共有的表观遗传特征，以及与SAD患者社交回避相关的独特表观遗传特征。有助于阐明这些疾病的表观遗传学基础。
