*Geek Box: Phenome-Wide Association Studies

*Geek Box: Phenome-Wide Association Studies

As a result of mapping the human genome, the technology is now available for research to analyse over a million genetic variants, known as “single nucleotide polymorphisms” [SNPs], and study the associations between those SNPs with health and disease. Such large-scale studies are known as “genome-wide association studies” [GWAS], as the associations are examined over the full human genome.

The basic premise of GWAS, however, is that the phenotype precedes the genotype, i.e., if we are interested in genetic underpinnings of cardiovascular disease, the analysis utilises a cohort of cases with that specific phenotype, i.e., with cardiovascular disease. One alternative that has emerged in the past decade is “phenome-wide association studies” [Phe-WAS], which has been termed a “reverse GWAS”.

For example, a Phe-WAS study utilises data across a range of human phenotypes, termed the “phenome”, to determine the range of associations with a specific given genotype. This has the advantage of identifying potential targets for therapies, new insights into disease mechanisms, and/or discovery of new genetic associations.

The major difference is in the nature of the associations; as GWAS already takes a specific disease phenotype, the genetic associations may not explain much of the overall phenotype. Thus, the conceptual benefit of Phe-WAS is that the specific genotype is associated with the phenotype in an unbiased manner. Both GWAS and Phe-WAS may be used complementarily, with Phe-WAS providing a means to replicate the genotype–phenotype associations identified in GWAS.