Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Psychiatry Clin Neurosci. 2015 Jul;69(7):388-401. doi: 10.1111/pcn.12291. Epub 2015 Apr 5.
This review provides a broad overview of the state of research in the genetics of anxiety disorders (AD). Genetic epidemiological studies report a moderate level of familial aggregation (odds ratio: 4-6) and heritability estimates are about 30-50%. Twin studies suggest that the genetic architecture of AD is not isomorphic with their classifications, sharing risk factors with each other. So far, linkage and association studies of AD have produced inconclusive results. Genome-wide association studies of AD can provide an unbiased survey of common genetic variations across the entire genome. Given the shared causes of AD that transcend our current diagnostic classifications, clustering anxiety phenotypes into broader groups may be a powerful approach to identifying susceptibility locus for AD. Using such a shared genetic risk factor, meta-analyses of genome-wide association studies of AD conducted by large consortia are needed. Environmental factors also make a substantial contribution to the cause of AD. Although candidate gene studies of gene by environmental (G × E) interaction have appeared recently, no genome-wide search for G × E interactions have been performed. Epigenetic modification of DNA appears to have important effects on gene expression mediating environmental influences on disease risk. Given that G × E can be linked to an epigenetic modification, a combination analysis of genome-wide G × E interaction and methylation could be an alternative method to find risk variants for AD. This genetic research will enable us to utilize more effective strategies for the prevention and treatment of AD in the near future.
这篇综述提供了焦虑障碍（AD）遗传学研究现状的广泛概述。遗传流行病学研究报告表明，AD 具有中度的家族聚集性（优势比：4-6），遗传度估计约为 30-50%。双胞胎研究表明，AD 的遗传结构与其分类并不相似，彼此之间存在共同的风险因素。到目前为止，AD 的连锁和关联研究尚未得出明确的结果。AD 的全基因组关联研究可以对整个基因组中的常见遗传变异进行无偏的调查。鉴于 AD 的共同病因超越了我们目前的诊断分类，将焦虑表型聚类为更广泛的组可能是识别 AD 易感基因座的有效方法。需要由大型联盟进行 AD 的全基因组关联研究的荟萃分析，以利用这种共同的遗传风险因素。环境因素也对 AD 的发病原因有很大的影响。尽管最近出现了基因与环境（G×E）相互作用的候选基因研究，但尚未进行全基因组搜索 G×E 相互作用。DNA 的表观遗传修饰似乎对介导环境对疾病风险影响的基因表达有重要影响。鉴于 G×E 可以与表观遗传修饰相关联，因此全基因组 G×E 相互作用和甲基化的组合分析可能是发现 AD 风险变异的另一种方法。这种遗传研究将使我们能够在不久的将来利用更有效的策略来预防和治疗 AD。
