Genome-wide association studies(GWASs) have identified thousands of genes and genetic variants(mainly SNPs) that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function,and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA methylation and mi RNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.
