Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Nat Rev Nephrol. 2020 Jul;16(7):377-390. doi: 10.1038/s41581-020-0278-5. Epub 2020 May 12.
Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular disease) and microvascular complications (such as diabetic kidney disease, diabetic retinopathy and neuropathy) lead to increased mortality, blindness, kidney failure and an overall decreased quality of life in individuals with diabetes. Clinical risk factors and glycaemic control alone cannot predict the development of vascular complications; numerous genetic studies have demonstrated a clear genetic component to both diabetes and its complications. Early research aimed at identifying genetic determinants of diabetes complications relied on familial linkage analysis suited to strong-effect loci, candidate gene studies prone to false positives, and underpowered genome-wide association studies limited by sample size. The explosion of new genomic datasets, both in terms of biobanks and aggregation of worldwide cohorts, has more than doubled the number of genetic discoveries for both diabetes and diabetes complications. We focus herein on genetic discoveries for diabetes and diabetes complications, empowered primarily through genome-wide association studies, and emphasize the gaps in research for taking genomic discovery to the next level.
糖尿病是全球增长最快的疾病之一，预计到 2045 年将影响 6.93 亿成年人。严重的大血管并发症（心血管疾病）和微血管并发症（如糖尿病肾病、糖尿病视网膜病变和神经病变）导致糖尿病患者死亡率增加、失明、肾衰竭和整体生活质量下降。临床危险因素和血糖控制本身不能预测血管并发症的发生；许多遗传研究表明，糖尿病及其并发症都有明显的遗传因素。早期旨在确定糖尿病并发症遗传决定因素的研究依赖于适用于强效应基因座的家族连锁分析、易产生假阳性的候选基因研究，以及受样本量限制的全基因组关联研究。新的基因组数据集的爆炸式增长，无论是生物库还是全球队列的聚集，都使糖尿病及其并发症的遗传发现数量增加了一倍以上。我们在此主要关注通过全基因组关联研究获得的糖尿病和糖尿病并发症的遗传发现，并强调在将基因组发现提升到一个新的水平方面研究存在的差距。
