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.