Shared genetic architecture across psychiatric disorders.
Shared genetic architecture across psychiatric disorders.
复制标题
跨精神病障碍共享遗传结构。
DOI：
10.1017/s0033291721000829
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发表时间：
2021-10
影响因子：
6.9
通讯作者：
Grotzinger, Andrew D.
中科院分区：
文献类型：
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作者：
Grotzinger, Andrew D.
精神疾病在基因水平上有很大的重叠，基于家庭的方法长期以来指向跨诊断风险途径。精神病学基因组学在过去十年中发展迅速，在多个层次的分析中揭示了交叉障碍风险的生物构成。已经发现了100多种影响多种疾病的遗传变异，随着样本量的不断增长，还有更多的基因变异有待发现。交叉障碍机制研究建立在这些发现的基础上，将跨诊断变异归类为有意义的类别，包括在哪些组织中或在发育中何时表达这些变异。在最高水平上，已经开发出方法来估计所有特征对之间的总体共享遗传信号(即，基于SNP的遗传相关性)，并随后对这些关系进行建模，以确定最主要的基因组风险因素。这些因素随后可以与外部特征(例如，功能成像表型)相关联，以开始了解这些跨诊断风险因素的构成。随着精神病学基因组学努力的继续扩大，我们可以通过包括更细粒度的表型(即症状水平数据)和明确考虑环境来开始获得更多的洞察力。这些努力的结果将有助于为我们目前的病因学提供自下而上的修订。
Psychiatric disorders overlap substantially at the genetic level, with family-based methods long pointing towards transdiagnostic risk pathways. Psychiatric genomics has progressed rapidly in the last decade, shedding light on the biological makeup of cross-disorder risk at multiple levels of analysis. Over a hundred genetic variants have been identified that affect multiple disorders, with many more to be uncovered as sample sizes continue to grow. Cross-disorder mechanistic studies build on these findings to cluster transdiagnostic variants into meaningful categories, including in what tissues or when in development these variants are expressed. At the uppermost level, methods have been developed to estimate the overall shared genetic signal across pairs of traits (i.e., SNP-based genetic correlations) and subsequently model these relationships to identify overarching, genomic risk factors. These factors can subsequently be associated with external traits (e.g., functional imaging phenotypes) to begin to understand the makeup of these transdiagnostic risk factors. As psychiatric genomic efforts continue to expand, we can begin to gain even greater insight by including more fine-grained phenotypes (i.e., symptom-level data) and explicitly considering the environment. The culmination of these efforts will help to inform bottom-up revisions of our current nosology.