Veterans Affairs Study Produces Genotype Assay for Major Diseases

In an ongoing genomic medicine study, a group of geneticists developed a six-part clinical genotype assay for the Department of Veterans Affairs. The new assay utilizes six polygenic risk scores (PRS) for diseases like diabetes, breast cancer, and other forms of cancer to generate odds ratios for disease risk. Results from the group’s recent study enable the inclusion of these assays into clinical workflows, improving the process of cancer detection and the practice of genomic testing.

To replicate polygenic risk scores, researchers experimented with the Massachusetts General Brigham Biobank, which contains 36,423 patient genetic records. The assay used in the study generated a robust disease odds ratio and was then transferred to the smaller population of subjects observed by the Veterans Affairs Genomic Medicine project.

The researchers included processes for workflow optimization in their findings and the strategy for dealing with a patient with a high PRS. The trial analyzed 227 genomes and detected two cases of cancer-causing genes. Researchers went on to work with doctors and counselors to contact each patient with a high-risk PRS result. Patients and their physicians also received a copy of the lab report. Each patient who scored highly on the assay was given patient-oriented educational materials about their relevant disease.

PRS are not diagnoses but instead a comparison between different genetic makeups between people. These scores are developed through statistical analysis of genomes and observed rates of disease. Generating a risk score is difficult, and it requires large genomic studies. Researchers in the Veterans Affairs study used six risk scores to create their assay; they chose each score based on its past success in confirming disease risk.

An example of one successful PRS is the association between breast cancer and the BRCA1 gene. Women who carry the BRCA1 gene are at higher risk of developing breast cancer, and doctors use that information to suggest treatment pathways that will reduce the lifetime risk of the disease.

As the study of molecular genetics matures and scientists identify other high-performing risk scores, the need grows for incorporating that information into the practice of medicine. EPIC Systems, the health IT vendor, has partnered with oncologists to build an accessible platform for genomic data. Their approach to supporting clinical workflows allows clinicians to order genomic tests electronically. This advancement will expand the conversation between patient and doctor and possibly assist with earlier cancer detection.

Currently, most genomic research and PRS are based on euro-centric populations or people with European ancestry. Because of this lack of diversity, minority patients may be missing out on the benefits of genomic research. Mayo Clinic researchers studied various types of cancer and found lower quality genomic sequencing for Black patients leading to underdetection of germline variants and less complete cancer data.

The diverse expansion of genomic testing produces a better understanding of the mechanisms behind some of the most debilitating diseases. For example, a UK Alzheimer’s study identified 42 new genes associated with an increased risk of disease. Using 600,000 healthy individuals from five countries, researchers identified additional genetic pathways for disease progression and the biological developments leading to worse manifestations of Alzheimer’s.

Moving forward, genomic testing will continue to rely on comprehensive genomic data and the diligent research needed to identify robust polygenic risk scores. Improvements will advance the process of cancer detection and the understanding of other genetic diseases like Alzheimer’s.