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Janet Gray, Ph.D.
Janet Gray, Ph.D.

As author of our 2008 and 2010 State of the Evidence reports, Dr. Gray drives the science behind all our work.

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Genome-Wide Association Studies


Definition: A genome-wide association study, or GWAS, involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental illnesses. (Source:

Classification: Genomic

New technologies like GWAS—in addition to helping us understand how the primary breast cancer genes, BRCA1 and BRCA2, contribute to breast cancer causation—allow molecular epidemiologists to scan broadly across the full genome to find possible genetic variations that are associated with disease states, including breast cancer (NHGRI, 2010).

GWAS approaches can concurrently examine thousands of gene variants and their association with particular disease (for example, breast cancer) and/or environmental exposures. Because the large number of gene variants associated with a disease or toxicant may lead to results that are difficult to interpret, scientists are turning to methods that combine results from multiple studies to validate results. They are also beginning to focus their analyses on particular genes and gene variants in particular cellular pathways that are known or presumed to be involved in susceptibility to diseases like breast cancer (Li 2011). One large international study recently identified over 75 common gene variants that were associated with an increased risk of breast cancer (Melcher, 2013); several other studies have confirmed some of these findings (Eccles, 2013)


In the large Collaborative Oncological Gene-environment Study, more than 200,000 SNPs (small sequences of DNA) were evaluated. In addition to the major breast cancer genes (BRCA1 and BRCA2) that have been well-associated with higher risk, several more moderately influential genes and over 25 new genetic loci of lower penetrance (found in fewer women) were identified. These data may help explain the variability in susceptibility to development of breast cancer, as well as the variability in how the disease is expressed (age of diagnosis, location, aggressiveness, receptor profile, responsiveness to treatment, etc.) (Michailidou, 2013).


The success of these methods for detecting associations between genetic markers and disease onset has led to great increases in the number of studies looking at these relationships. This has enhanced our understanding of genetic variability. These approaches have the potential to deepen our understanding of the variability of sensitivity to environmental factors that are found in individuals and populations with different vulnerabilities to developing breast cancer.


The contributions of individual genetic variants are often fairly weak and may not take into account interactions with other non-genetic factors. Most of the focus of these studies is on better understanding the various genetic factors, beyond BRCA1 and BRCA2, that are important in the etiology of familial breast cancer, which accounts for approximately 5-7 percent of all breast cancer cases (Melchor, 2013; Sakoda, 2013). To date, this approach is less helpful for understanding the interactions between non-heritable genetic abnormalities and interactions between genetic and other (e.g., environmental exposures) factors that increase risk for breast cancer. However, newer approaches are now being developed and tested to examine how genes and the environment interact using GWAS and other large-array technologies (Schoeps, 2013; Thomas, 2012).