The Hunt for Low-Frequency Alleles Predisposing to Type 2 Diabetes and Related Cardiovascular Risk Factors

摘要

Research into the genetic basis of cardiovascularrelated diseases is moving at an extremely fast pace. Developments in technology such as whole-genome sequencing and massive resources of DNA collected from hundreds of thousands of people mean scientists have an unprecedented ability to discover the genetic variation that predisposes to disease. Before 2007, very little was known about the variation in the human DNA sequence and its influence on common diseases. We now know of hundreds of common variants that influence LDL cholesterol levels, type 2 diabetes, hypertension and heart disease to name a few. Attention has now turned to the discovery of the genetic variants that occur in between 1 in 20 and 1 in 1000 individuals. These variants are unlikely to cause disease in the same way that mutations in some genes cause a monogenic disorder with a particular pattern of inheritance. But variants in this frequency range will shed light on biological mechanisms of disease. In this review, we focus on these variants and discuss how a range of study designs have identified low-frequency genetic variants with stronger predisposing effects on type 2 diabetes and related traits than common genetic variants.