GWAS signals in or near protein-coding regions, and even stronger evidence for overrepresentation of SNPs in certain noncoding regions (Hindorff et al., 2009). Once considered “junk DNA”, it is now known that many regions outside of the exons that code for proteins have an indirect biological effect through the regulation of when, in what tissue, and under what circumstances a gene is expressed (ENCODE Project Consortium, 2012). Epigenetic factors near the transcription start site of a gene and in other key regulatory regions can influence gene expression by changing the physical conformation of the DNA, thus changing how accessible the DNA is to the cellular machinery responsible for transcribing genes into proteins.
