Genetics of T2DM and Its Chronic Complications: Are We Any Closer to the Individual Prediction of Genetic Risk?

Abstract

Type 2 diabetes mellitus (T2DM) is a complex disease that has risen in global prevalence over recent decades, resulting in concomitant and enormous socio-economic impacts. In addition to the well-documented risk factors of obesity, poor dietary habits and sedentary lifestyles, genetic background plays a key role in the aetiopathogenesis of diabetes and the development of associated micro- and macrovascular complications. Recent advances in genomic research, notably next-generation sequencing and genome- wide association studies, have greatly improved the efficiency with which genetic backgrounds to complex diseases are analysed. To date, several hundred single-nucleotide polymorphisms have been associated with T2DM or its complications. Given the polygenic background to T2DM (and numerous other complex diseases), the degree of genetic predisposition can be treated as a "continuous trait" quantified by a genetic risk score. Focusing mainly on the Central European population, this review summarizes recent state-of-the-art methods that have enabled us to better determine the genetic architecture of T2DM and the utility of genetic risk scores in disease prediction.