Genome-Wide Association Studies (GWAS)

 Genome-wide association studies (GWAS) are designed to find associations between genomic variants and a phenotype, usually a complex multifactorial disease. The idea for association studies in a large cohort was floated after linkage analysis, which proved extremely successful in the identification of causative genes for rare disorders, but it did not come up to expectations in the case of common complex disorders where causative alleles are less frequently aggregated in families. Ever since their advent in 2005, GWAS have transformed gene identification ventures in complex disease genetics over the past fifteen years, giving rise to several powerful associations for complex traits and disorders. Association studies are based on the “common disease common variant” hypothesis which assumes that genomic variation with low penetrance and high population frequency are involved in the causation of common complex disorders. Although GWAS, complemented with the downstream functional assessment of the variants, have been successful in identifying novel disease-causing genes and biological mechanisms, the field has also received intense criticism over the years, especially its failure in tracing the so-called ‘missing heritability’. Therefore, further functional studies are mandatory to precisely establish a link between risk alleles and a phenotype. This chapter broadly covers an introduction of GWAS, their successes and limitations, and various important factors affecting the design and results, followed by challenges in the post-GWAS era.

Keywords: Genome-wide Association Studies, Linkage Disequilibrium, Multifactorial Diseases, Missing Heritability, SNPs, WGS.