Polygenic risk scores in psychiatry: Will they be useful for clinicians?
Polygenic risk scores in psychiatry: Will they be useful for clinicians?
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DOI：
10.12688/f1000research.18491.1
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Nurnberger, John I
中科院分区：
文献类型：
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作者：
Fullerton, Janice M;Nurnberger, John I
主要的精神疾病是遗传的，但它们在基因上是复杂的。这意味着，除了某些例外，单基因标记对诊断没有帮助。然而，我们正在更多地了解大量的基因变异，这些基因变异与精神分裂症、双相情感障碍和其他精神疾病的风险有关。这些风险变异的存在现在可以组合成多基因风险评分（PRS）。这样的评分提供了个体中风险变体的基因组负担的定量指数，其涉及一个人患有特定病症的可能性。目前，这些分数在研究中非常有用，它们告诉我们很多关于不同疾病和其他大脑功能指标之间的关系。未来，随着支持这些评分的数据集变得更大、更多样化，以及方法学的发展提高了预测能力，我们预计PRS将在评估疾病风险、疾病亚型甚至治疗反应方面具有实质性的临床实用性。在这里，我们提供了一个概述PRS的一般条款（包括一个词汇表适合知情的非遗传学家），并讨论了PRS在精神病学中的使用，包括其局限性和解释的注意事项，以及他们的应用程序现在和将来。
Major psychiatric disorders are heritable but they are genetically complex. This means that, with certain exceptions, single gene markers will not be helpful for diagnosis. However, we are learning more about the large number of gene variants that, in combination, are associated with risk for disorders such as schizophrenia, bipolar disorder, and other psychiatric conditions. The presence of those risk variants may now be combined into a polygenic risk score (PRS). Such a score provides a quantitative index of the genomic burden of risk variants in an individual, which relates to the likelihood that a person has a particular disorder. Currently, such scores are quite useful in research, and they are telling us much about the relationships between different disorders and other indices of brain function. In the future, as the datasets supporting the development of such scores become larger and more diverse and as methodological developments improve predictive capacity, we expect that PRS will have substantial clinical utility in the assessment of risk for disease, subtypes of disease, and even treatment response. Here, we provide an overview of PRS in general terms (including a glossary suitable for informed non-geneticists) and discuss the use of PRS in psychiatry, including their limitations and cautions for interpretation, as well as their applications now and in the future.