Genomics era and complex disorders: Implications of GWAS with special reference to coronary artery disease, type 2 diabetes mellitus, and cancers

Abstract

The Human Genome Project (HGP) has identified millions of single nucleotide polymorphisms (SNPs) and their association with several diseases, apart from successfully characterizing the Mendelian/monogenic diseases. However, the dissection of precise etiology of complex genetic disorders still poses a challenge for human geneticists. This review outlines the landmark results of genome-wide association studies (GWAS) with respect to major complex diseases - Coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and predominant cancers. A brief account on the current Indian scenario is also given. All the relevant publications till mid-2015 were accessed through web databases such as PubMed and Google. Several databases providing genetic information related to these diseases were tabulated and in particular, the list of the most significant SNPs identified through GWAS was made, which may be useful for designing studies in functional validation. Post-GWAS implications and emerging concepts such as epigenomics and pharmacogenomics were also discussed.

Figure 1

Schematic diagram of events contributing to the development of genomics

Figure 2

Histogram representing the number of GWAS and SNPs associated with each complex disease

Figure 3

Prevalence and death rates due to major cancers reported in the year 2012

Figure 4

Chromatin features and epigenetic markers of active euchromatin and repressed heterochromatin (adapted from reference 75)