Timpson Nicholas John, Dudbridge Frank
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Health Sciences, University of Leicester, Leicester, UK.
Wellcome Open Res. 2018 Oct 31;3:138. doi: 10.12688/wellcomeopenres.14870.1. eCollection 2018.
Initial genomewide association studies were exceptional owing to an ability to yield novel and reliable evidence for heritable contributions to complex disease and phenotype. However the top results alone were certainly not responsible for a wave of new predictive tools. Despite this, even studies small by contemporary standards were able to provide estimates of the relative contribution of all recorded genetic variants to outcome. Sparking efforts to quantify heritability, these results also provided the material for genomewide prediction. A fantastic growth in the performance of human genetic studies has only served to improve the potential of these complex, but potentially informative predictors. Prompted by these conditions and recent work, this letter explores the likely utility of these predictors, considers how clinical practice might be altered through their use, how to measure the efficacy of this and some of the potential ethical issues involved. Ultimately we suggest that for common genetic variation at least, the future should contain an acceptance of complexity in genetic architecture and the possibility of useful prediction even if only to shift the way we interact with clinical service providers.
最初的全基因组关联研究非常出色，因为它有能力为复杂疾病和表型的遗传贡献提供新颖且可靠的证据。然而，仅凭顶尖的研究结果肯定无法催生一波新的预测工具。尽管如此，即使是按照当代标准规模较小的研究，也能够对所有记录的基因变异对结果的相对贡献进行估计。这些结果激发了人们对量化遗传力的努力，也为全基因组预测提供了素材。人类遗传学研究性能的惊人增长，只会提升这些复杂但可能具有信息价值的预测指标的潜力。受这些情况和近期研究工作的启发，本信函探讨了这些预测指标可能具有的效用，考虑了通过使用它们临床实践可能会如何改变，如何衡量其效果以及其中涉及的一些潜在伦理问题。最终，我们认为至少对于常见的基因变异而言，未来应该接受遗传结构的复杂性以及有用预测的可能性，即便这只是为了改变我们与临床服务提供者互动的方式。
