常见疾病比核心基因全基因组模型所暗示的更为复杂。

Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model.

机构信息

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia.

University of Groningen, University Medical Center Groningen, Department of Genetics, P.O. Box 30001, 9700 RB Groningen, Netherlands.

出版信息

Cell. 2018 Jun 14;173(7):1573-1580. doi: 10.1016/j.cell.2018.05.051.

DOI:10.1016/j.cell.2018.05.051

PMID:29906445

Abstract

The evidence that most adult-onset common diseases have a polygenic genetic architecture fully consistent with robust biological systems supported by multiple back-up mechanisms is now overwhelming. In this context, we consider the recent "omnigenic" or "core genes" model. A key assumption of the model is that there is a relatively small number of core genes relevant to any disease. While intuitively appealing, this model may underestimate the biological complexity of common disease, and therefore, the goal to discover core genes should not guide experimental design. We consider other implications of polygenicity, concluding that a focus on patient stratification is needed to achieve the goals of precision medicine.

摘要

大量证据表明，大多数成年发病的常见疾病具有多基因遗传结构，这与多种后备机制支持的强大生物系统完全一致。在此背景下，我们考虑最近的“全基因组”或“核心基因”模型。该模型的一个关键假设是，与任何疾病相关的核心基因数量相对较少。虽然这个模型直观上很有吸引力，但它可能低估了常见疾病的生物学复杂性，因此，发现核心基因的目标不应该指导实验设计。我们考虑了多基因性的其他影响，得出的结论是，需要关注患者分层，以实现精准医学的目标。