Genome Wide Association Study

What is a Genome Wide Association Study (GWAS)?

A genome wide association study attempts to better understand how specific genetic mutations or alleles correlate with incidence or severity of a disease or other patient phenotype. They typically involve large datasets of patient-level data including both genetic and phenotypic (clinical and demographic characteristics) variables. The UK Biobank is a particularly famous example that continues to be used in support of drug development including identification of new targets for the treatment of specific disease.

As with other large, observational datasets one of the challenges in using GWAS for target identification is in separating correlation from potential causal effects, especially due to the high potential for confounding. Nonetheless, when applied rigorously and with further studies to validate findings, GWAS can be a powerful part of the discovery armamentarium.

One of the bigger success stories when it comes to use of GWAS studies to support drug development is in identification of the PCSK9 gene and the realization that patients who have mutations in it have much lower levels of LDL cholesterol and in turn, cardiovascular events. The original studies eventually led to development and approval of targeted therapies which inhibit PCSK9, lower LDL, and reduce events in patients.