Some of the first results from the Alabama Genomic Health Initiative (AGHI)were recently published in Genetics in Medicine. The AGHI, launched in 2017, is one of the nation's first statewide efforts to harness the power of genomic analysis to find answers for children and adults with undiagnosed developmental and medical challenges, and to identify individuals who are at a higher risk for developing certain diseases in the future.
The program, which is a collaboration between the HudsonAlpha Institute for Biotechnology and the University of Alabama at Birmingham, provides genomic testing, interpretation and counseling free of charge to Alabama residents. The goal is to engage at least 10,000 Alabamians in genetic testing, while educating the participants about their genomic health.
"AGHI is helping to improve patient care, not only by providing diagnoses, but also by giving the general public a foundational understanding of the importance of being informed about their genomic health," said Greg Barsh, MD, PhD, senior scientist at HudsonAlpha . "Through AGHI, we are able to provide an opportunity to physicians and geneticists to confirm or identify a diagnosis that has gone undiagnosed despite a vast array of previous medical testing."
AGHI engages two groups of participants in Alabama: children and adults with undiagnosed rare disease, and adults in the general population who do not have a significant personal or family history suggestive of a genetic condition. The published data reflects the first 176 rare-disease participants and 5,369 participants in the population screening group.
Participants, who were recruited across the state, provided a blood sample, as well as information about their personal and family health history. DNA was extracted from the blood sample and analyzed. Participants in the population screening group received a genotyping test, while participants in the rare-disease group received genome sequencing. Genotyping tests look at a preselected group of variants that are known to increase a person's likelihood of disease, while whole-genome sequencing looks at every single letter of the genetic code.
Participants received a report summarizing their test results. Individuals whose results include actionable findings received genetic counseling and a referral to appropriate medical care.
"We speak by phone with participants who have an identified genetic risk factor," said co-author Whitley Kelley, a genetic counselor at HudsonAlpha. "We explain what it means to have a genetic risk factor. Then we provide recommendations for clinical resources that can guide their next steps in prevention and personalized health management. It is important to us to make sure the participants understand their results."
In the rare-disease group, of the 176 affected individuals, 35 (19.9 percent) received a pathogenic or likely pathogenic result, meaning a genetic variant was found that is believed to contribute to disease. In addition, 42 individuals (23.9 percent) received an uncertain result, meaning a genetic variant was found that is not well understood, but may contribute to disease. The new genetic knowledge, combined with the individual's symptoms, often allows doctors to make a diagnosis for a disease that had remained undiscovered for months or years.
To date, 5,369 individuals, representing all 67 Alabama counties, have been enrolled in the population screening group of AGHI. 81 positive genotyping results among 80 individuals (1.5 percent) were identified in the population cohort. These results include risk-increasing variants for hereditary cancer, cardiomyopathy, malignant hyperthermia and hypercholesterolemia.