Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Endocr Rev. 2019 Dec 1;40(6):1500-1520. doi: 10.1210/er.2019-00088.
During the last decade, there have been substantial advances in the identification and characterization of DNA sequence variants associated with individual predisposition to type 1 and type 2 diabetes. As well as providing insights into the molecular, cellular, and physiological mechanisms involved in disease pathogenesis, these risk variants, when combined into a polygenic score, capture information on individual patterns of disease predisposition that have the potential to influence clinical management. In this review, we describe the various opportunities that polygenic scores provide: to predict diabetes risk, to support differential diagnosis, and to understand phenotypic and clinical heterogeneity. We also describe the challenges that will need to be overcome if this potential is to be fully realized.
在过去的十年中，人们在鉴定和描述与 1 型和 2 型糖尿病个体易感性相关的 DNA 序列变异方面取得了重大进展。这些风险变异与提供有关疾病发病机制中涉及的分子、细胞和生理机制的见解相结合，当它们组合成多基因评分时，可以捕获有关个体疾病易感性模式的信息，这些信息有可能影响临床管理。在这篇综述中，我们描述了多基因评分提供的各种机会：预测糖尿病风险、支持鉴别诊断以及了解表型和临床异质性。我们还描述了如果要充分实现这一潜力，将需要克服的挑战。
