Phenome-Wide Association Studies

Abstract

Genome-wide association studies (GWAS) have made clear that single-nucleotide variants (SNVs) that occur at multiple locations across the genome can be associated with a specific condition or trait, also known as a phenotype. Phenome-wide association studies (PheWAS) invert the idea of a GWAS by searching for phenotypes associated with specific SNVs across the range of thousands of human phenotypes, or the “phenome” (Figure). Analogous to GWAS, PheWAS have shown that specific genetic variations may be associated with multiple conditions and traits.

Figure.. Genome-Wide Association Study (GWAS) Compared With Phenome-Wide Association Study (PheWAS)

A GWAS (top) contrasted with a PheWAS (bottom). A GWAS starts with families or populations in which individuals have been assigned affected or unaffected status for a disease or other trait, such as a complication of a disease or an adverse outcome during drug treatment, and searches for associated genetic variants. A PheWAS starts with a genetic variant and searches across a set of curated human phenotypes (the “phenome”) to identify associated phenotypes. The “input function” for the PheWAS can be a single genetic variant or sets of variants or other traits.