Meta-Analysis of Genome-Wide Association Studies to Understand Disease Relatedness

Abstract

Genome-wide association studies (GWAS) have become a popular method of surveying haplotype variations within populations. The recent explosion and success of these studies has allowed for identification of multiple gene variations and non-genetic risk factors that are often involved in pathogenesis of many diseases (XavierR The International HapMap Consortium, 2007) and development of GWAS databases (Johnson&O'Donnell, 2009) such as Genomes.gov (Hindorff et al., 2009). The HapMap database of genetic variants and the ever progressing technology involved in identifying genetic disease susceptibility markers has allowed for identification of shared genetic associations that were undetectable with previous methods for identifying deleterious mutations effects for individual genes (Xavier&Rioux, 2008). We are now capable of detecting common susceptibility markers between previously unassociated diseases with the ability to assess combined association signals shared by biological pathways (Wang et al., 2011). Research of immune-mediated disease susceptibility has benefited from the discovery of shared haplotypes. GWAS with a focus on autoimmune diseases, which included celiac disease, Crohn’s disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes (Lettre&Rioux, 2008), have shed light on shared genetic markers. Such markers can be exploited to identify biomedical traits that translate to improved diagnostic and treatment techniques (McCarthy et al., 2008). Under the common disease/common variant hypothesis (Wang et al., 2005), one would assume that shared variants result in shared disease phenotypes, and this commonality could serve as a global target for effective treatment options. It is under this assumption that many disease association studies are conducted. The Wellcome Trust Case Control Consortium (WTCCC) conducted a study in which nearly 2000 individuals were examined for coronary artery disease (CAD), hypertension, type II diabetes (T2D), rheumatoid arthritis (RA), Crohn’s disease (CD), type I diabetes (T1D) and bipolar disorder (BD) susceptibility against a shared set of about 3000 controls (The Wellcome Trust Case Control Consortium, 2007). The study revealed several association loci for the seven diseases, with some of these indicating risk for more than one of the studied diseases (The Wellcome Trust Case Control Consortium, 2007).