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The rising global prevalence of diabetes mellitus is accompanied by an increasing burden of morbidity and mortality that is attributable to the complications of chronic hyperglycaemia. These complications include blindness, renal failure and cardiovascular disease. Current therapeutic options for chronic hyperglycaemia reduce, but do not eradicate, the risk of these complications. Success in defining new preventative and therapeutic strategies hinges on an improved understanding of the molecular processes involved in the development of these complications. This Review explores the role of human genetics in delivering such insights, and describes progress in characterizing the sequence variants that influence individual predisposition to diabetic kidney disease, retinopathy, neuropathy and accelerated cardiovascular disease. Numerous risk variants for microvascular complications of diabetes have been reported, but very few have shown robust replication. Furthermore, only limited evidence exists of a difference in the repertoire of risk variants influencing macrovascular disease between those with and those without diabetes. Here, we outline the challenges associated with the genetic analysis of diabetic complications and highlight ongoing efforts to deliver biological insights that can drive translational benefits.

Original publication

DOI

10.1038/nrneph.2015.37

Type

Journal article

Journal

Nat Rev Nephrol

Publication Date

05/2015

Volume

11

Pages

277 - 287

Keywords

Animals, Coronary Artery Disease, Diabetes Complications, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Diabetic Neuropathies, Diabetic Retinopathy, Epigenomics, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Kidney Failure, Chronic, Peripheral Arterial Disease