In recent years, the genome-wide association study (GWAS) approach has led to the identification of many genetic associations for common complex traits.37 This model-free approach to gene discovery has led to a greater pathophysiologic understanding of many disorders, although only small proportions of the total genetic variance have so far been explained, and many of the identified variants have not brought new biological understanding.38 To address the latter concern, functional support for GWAS findings has been sought by determining their effects on gene expression (expression quantitative trait loci- eQTLs) and methylation level (methylation quantitative trait loci-mQTLs).38 Top single nucleotide polymorphisms (SNPs) have also been examined for potential enrichment of eQTLs and mQTLs, compared to expected rates. Moreover, examination for over-representation of micro-RNA (miRNA) binding sites has also been adopted as an informative approach,39 given the role of miRNA in regulating gene expression. In addition, pathway analyses have been conducted to determine whether specific gene pathways are enriched among the strongest associated variants.40
