Using epigenetic mechanisms to understand the impact of common disease causing alleles

Abstract

Many common genetic variants have been identified to be associated with autoimmune diseases such as Type I diabetes. Methods to identify these genetic loci have become powerful, but deciphering the functional effects of these variants in disease progression remains a major challenge. Recent studies have shown that single nucleotide polymorphisms are associated with altered DNA methylation and chromatin accessibility, suggesting that genetic variants can alter epigenetic features and epigenetic variations can mediate genetic variability. In this review, we highlight recent studies that have examined the relationship between genetics and epigenetics, and how epigenetic studies may complement genetic studies in understanding the impact of common disease causing alleles.

Figure 1. Epigenetic Mechanisms and Variants

Genetic variants (yellow stars) are associated with differences in: (A) DNA methylation (white lollipops represent CpGs and brown lollipops represent methylated CpGs), (B) binding of proteins to DNA which can alter recruitment of chromatin modifiers (yellow circle represents DNA-binding protein such as transcription factor and pink oval represents chromatin modifier), and (C) chromatin organization (red, blue, and orange spheres represent DNA-binding proteins and co-factors associated with DNA). (D) Variants found in long non-coding RNAs (light blue represent RNA with secondary structure and purple, brown, green spheres represent proteins recruited by RNA to DNA) alter recruitment of chromatin modifiers to DNA. For each scenario, the genetic variants are influencing the expression of the proximal gene.