Harvard Medical School, Boston, USA.
Division of General Internal Medicine, Massachusetts General Hospital, 100 Cambridge St 16th Floor, Boston, MA, 02114, USA.
Curr Diab Rep. 2019 Jul 22;19(8):62. doi: 10.1007/s11892-019-1173-y.
Genome-wide association studies have delineated the genetic architecture of type 2 diabetes. While functional studies to identify target transcripts are ongoing, new genetic knowledge can be translated directly to health applications. The review covers several translation directions but focuses on genomic polygenic scores for screening and prevention.
Over 400 genomic variants associated with T2D and its related quantitative traits are now known. Genetic scores comprising dozens to millions of associated variants can predict incident T2D. However, measurement of body mass index is more efficient than genetic scores to detect T2D risk groups, and knowledge of T2D genetic risk alone seems insufficient to improve health. Genetically determined metabolic sub-phenotypes can be identified by clustering variants associated with physiological axes like insulin resistance. Genetic sub-phenotyping may be a way forward to identify specific individual phenotypes for prevention and treatment. Genomic polygenic scores for T2D can predict incident diabetes but may not be useful to improve health overall. Genetic detection of T2D sub-phenotypes could be useful to personalize screening and care.
全基因组关联研究已经描绘出 2 型糖尿病的遗传结构。虽然正在进行鉴定靶转录本的功能研究，但新的遗传知识可以直接转化为健康应用。本文综述了几个翻译方向，但重点是基因组多基因评分在筛查和预防中的应用。
目前已经发现了 400 多个与 T2D 及其相关数量性状相关的基因组变异。由数十到数百万个相关变异组成的遗传评分可以预测 T2D 的发生。然而，测量体重指数比遗传评分更能检测到 T2D 风险组，而且仅了解 T2D 的遗传风险似乎不足以改善健康。通过聚类与胰岛素抵抗等生理轴相关的变异，可以确定遗传决定的代谢亚表型。遗传亚表型分析可能是识别特定个体表型以进行预防和治疗的一种方法。用于 T2D 的基因组多基因评分可以预测新的糖尿病发生，但可能对整体健康改善没有用处。T2D 亚表型的遗传检测可能有助于个性化筛查和护理。
