Scientists have discovered that patients with peripheral artery disease who share certain genetic traits may be at higher risk for limb amputation, opening the door to early intervention before symptoms become severe. A new study from Northeastern University found 38 genetic variations associated with serious complications of the condition, suggesting that genetic testing could one day help doctors identify which of the millions of Americans with peripheral artery disease will need preventive treatment.

What Is Peripheral Artery Disease and Why Does It Matter?

Peripheral artery disease (PAD) is a common circulatory condition in which arteries in the legs, arms, and pelvis become partially or completely blocked due to plaque buildup. The condition affects approximately 10 million to 12 million people in America, but doctors currently have no reliable way to predict which patients will develop serious complications. The stakes are high: approximately 150,000 leg amputations are performed in the United States each year as a result of PAD, according to the American Heart Association.

The challenge is timing. By the time patients start experiencing pain in their arms and legs, the disease may have progressed too far to save their limbs. This is where the new genetic research could make a real difference.

How Did Researchers Identify These Genetic Risk Factors?

Researchers at Northeastern University conducted what's called a genome-wide association study (GWAS), a method that surveys medical databases of patients' DNA to identify genetic variants associated with a specific disease. The team analyzed thousands of patient files from the National Institutes of Health's All of Us Research Program, a large dataset initiative designed to collect health information from thousands of willing residents across the country to advance targeted health care treatments.

In their analysis, the researchers found 38 suggestive genetic variations, which are unique characteristics in someone's DNA that suggest a potentially increased chance of having a severe enough case of PAD that might result in limb loss. These variants were already known to be associated with important functions in the body, including the structure of blood vessels and capillaries and inflammatory regulation.

"This is powerful because you won't have to wait for symptoms. It will allow us to give treatment before the patients start suffering and could basically prevent amputation," said Saeed Amal, a research professor of bioengineering at Northeastern University's Roux Institute.

Saeed Amal, Research Professor of Bioengineering, Northeastern University

What Are the Next Steps for This Research?

While the findings are promising, researchers acknowledge significant limitations. The study only had access to data from the NIH's All of Us Program, meaning the results have not yet been proven to work across different populations or healthcare systems. To validate their findings, Amal and his team plan to collaborate with major healthcare providers across the country.

The validation process will involve several key steps:

• University of California San Diego Health: Researchers will examine patient databases from the university's foot and ankle care center to see if they can predict which patients will have an amputation based on genetic profiles.
• Maine Medical Center: Additional collaboration to test findings across different patient populations and geographic regions.
• MedStar Georgetown University Hospital: Further validation to ensure the genetic predictions hold true across diverse healthcare settings.

According to Michael Wilczek, a Northeastern professor of biotechnology and bioinformatics who assisted with the research, this work "lays the foundation" for more targeted healthcare treatments for PAD patients. The goal is to enable what's called precision medicine, an approach where an individual's healthcare plan is highly targeted and specific based on their own personal data.

How Could This Change Treatment for PAD Patients?

If validated across larger and more diverse populations, genetic testing could transform how doctors approach peripheral artery disease. Instead of waiting for patients to develop symptoms, physicians could identify high-risk individuals early and offer preventive medications or procedures before complications develop. This shift from reactive to proactive care could prevent thousands of amputations annually.

The research also highlights an important gap in our current understanding of PAD. While scientists have long known that risk factors such as smoking and poor diet can lead to a PAD diagnosis, the role genetics play in the onset and progression of the disease has remained unclear. This study begins to fill that knowledge gap, suggesting that genetic predisposition plays a meaningful role in determining who will develop severe disease.

As Amal noted, the ultimate goal is straightforward: "We want to provide medications or procedures that will prevent amputations". With continued collaboration and validation across multiple healthcare systems, genetic testing for PAD risk could become a standard part of cardiovascular screening within the next several years, potentially saving limbs and improving quality of life for millions of Americans living with this common circulatory condition.

As Amal