Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.

中文翻译：

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后GWAS时代恐慌症的遗传和表观遗传分析。

惊恐障碍 (PD) 是一种常见且使人衰弱的神经精神疾病，其特征是惊恐发作和过度焦虑。遗传因素和环境因素在 PD 发病机制和治疗反应中都起着重要作用。然而，PD 具有临床异质性和遗传复杂性，该疾病的确切遗传或环境原因尚不清楚。最近已经提供了各种检测致病基因的方法。特别是全基因组关联研究 (GWAS) 已引起人们对多因素疾病的疾病相关基因座的鉴定的关注。本综述介绍了 PD 的 GWAS，随后讨论了 GWAS 的局限性以及后 GWAS 时代遗传学家面临的主要挑战。然后提出了应对这些挑战的替代策略，例如使用下一代测序的表观基因组关联研究 (EWAS) 和罕见变异关联研究 (RVAS)。然而，迄今为止，很少有报告描述这些分析，证据仍然不足以自信地识别或排除 PD 中的罕见变异或表观遗传变化。因此需要进一步分析，使用数以万计的样本量、广泛的功能注释和高度针对性的假设检验。