Planning a genome-wide association study: points to consider

Abstract

It is well established that genetic diversity combined with specific environmental exposures contributes to disease susceptibility. However, it has turned out to be challenging to isolate the genes underlying the genetic component conferring susceptibility to most complex disorders. Traditional candidate gene and family-based linkage studies, which dominated gene discovery efforts for many years, were largely unsuccessful in unraveling the genetics of these traits due to the relatively limited information gained. Within the last 5 years, new advances in high-throughput methods have allowed for large volumes of single nucleotide polymorphisms (SNPs) throughout the genome to be genotyped across large and comprehensively phenotyped patient cohorts. Unlike previous approaches, these 'genome-wide association studies' (GWAS) have extensively delivered on the promise of uncovering genetic determinants of complex diseases, with hundreds of novel disease-associated variants being largely replicated by independent groups. This review provides an overview of these recent breakthroughs in the context of the pitfalls and challenges related to designing and carrying out a successful GWAS.