As Easy as ABC: From GWAS to Genes to Disease

By Adrienne Mueller, PhD
April 14, 2021

Since the completion of the human genome in the early 2000s, researchers have made big strides in their efforts to determine the relationship between genes and disease. Genome-wide association studies (GWAS) are a powerful approach that scans the genomes of many individuals to find common markers associated with a specific disease. The identified GWAS markers are often located in non-coding regions of the genome called “enhancers.” Enhancers are not genes themselves, but influence the expression of disease-related genes far away. Identifying which genes an enhancer influences is challenging in its own right, but it is made even more difficult by the fact that enhancers work differently in different cell types.

Jesse Engreitz, PhD, newly appointed Assistant Professor in Genetics and the Basic Science and Engineering Initiative, as well as the Cardiovascular Institute at Stanford, recently led a project developing a model that overcomes these challenges. As reported in Nature and a communication by the Broad Institute, the ABC model connects over 5000 genetic variants to nearly 2250 genes across 72 traits and diseases - including heart disease and cancer. Dr. Engreitz states, “We now have the ability to look comprehensively across many cell types and, for the first time, make reasonably accurate predictions of what these non-coding enhancers and variants do.”  The ABC model will accelerate our interpretation of GWAS markers and pave the way for a better understanding of how a person’s specific genome influences disease.