Did you know that genetic testing can help you understand your genetic risk for common diseases? Polygenic risk scores (PRS) allow us to estimate your inherited predisposition to complex diseases that affect millions of people annually, including cancer, dementia, and diabetes.

How Does Polygenic Risk Scoring (PRS) Work? 

When geneticists look for monogenic disorders, we look at your individual gene variants to understand your probability of developing the disorder. With polygenic risk scoring, we look at the cumulative effects of hundreds to thousands of common genetic variants. On their own, each of these common gene variants has modest effects on disease risk and health. Together, they can shape your susceptibility to complex disease throughout your life. 

How Well Do Polygenic Risk Scores Predict Disease? 

Polygenic risk scores (PRS) reflect your risk that exists from birth. However, these scores only tell us the probability of disease. They are not deterministic and do not provide any diagnosis or certainty that you will develop a condition. High genetic risk does not guarantee disease, and average risk does not guarantee protection. There are still many other factors, from your family history to your lifestyle, that influence your overall risk.

Unfortunately, PRS also has reduced predictive value for those with non-European ancestry. This is because PRS scores have been developed based on genome studies using populations with European ancestry. Thankfully, the science is evolving. While gaps remain, population studies are not only growing but expanding to include multiple ancestry groups. As this happens, risk scores may be recalculated to match current knowledge. (That’s why our clinic regularly reanalyzes our results to inform the guidance we give patients.)

Polygenic vs. Overall Risk: What Else Impacts My Disease Risk?

A polygenic risk score alone is not enough to guide clinical recommendations. Genetic risk is just one layer of your overall risk. 

For a full picture of risk and useful health recommendations, scores must be interpreted alongside your lifestyle and family history. (When we talk about lifestyle, we mean things like your diet, physical activity, smoking status, alcohol consumption, sleep quality, and stress levels. These are the areas with the greatest opportunity to change.) Clinical measurements, such as blood pressure, glucose, and lipid profile, provide further information. Analyzing your polygenic risk score in this complete context gives us more valuable and actionable insights. 

As you think about disease risk, know that PRS does not replace a detailed family history assessment. Regardless of PRS, if you or your doctor suspect you have an inherited or rare genetic disorder, genetic counseling and testing are vital. Even if you have low genetic risk, you should always follow standard preventive care and screening recommendations.

How Can Knowing My Genetic Risk Help Me?

Knowing your risk level can empower you to make changes to your life and behavior that reduce your overall risk. We use PRS only for conditions where actionable preventive interventions are possible. Understanding your overall risk (including your genetic risk) can motivate you to adopt healthier behaviors, start regular screenings and preventive medications if needed, and sustain these changes over time. Here are some examples of areas where knowing genetic risk can help patients.

Cardiovascular Disease Risk

Patients with known cardiovascular disease risk can talk with their doctor about:

  • Making diet and lifestyle changes
  • Taking statins at a younger age or lower risk threshold
  • More closely monitoring blood pressure
  • Considering earlier or more frequent cardiovascular risk assessment, including lipid profiles, coronary artery calcium scoring, and functional testing

Alzheimer’s and Dementia Risk

In coordination with their health care team, patients at increased risk for Alzheimer’s and dementia may choose to:

  • Monitor and more aggressively manage cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) that can contribute to dementia risk
  • Reduce dementia risk by focusing on physical activity, cognitive engagement, social connection, sleep optimization, and following a Mediterranean-style diet 
  • Do a neurocognitive baseline assessment and periodic monitoring (detecting changes early enables timely intervention and planning)
  • Enter clinical trials targeting presymptomatic disease-modifying therapy

Cancer Risk

  • PRS may inform when you start screening for certain cancers, the type or frequency of screening you receive, and whether you should seek chemoprevention.

PRS at SequenceMD: What to Expect

If you’re interested in polygenic risk scoring from SequenceMD, you’ll start with a baseline assessment and genetic counseling. The assessment will cover your family history, clinical data, social support systems, lifestyle, and more. In genetic counseling, you’ll discuss possible outcomes, ask any questions you have, and make sure you give informed consent before moving forward with genetic testing. We will then collect a saliva or blood sample to be sent to a lab for processing. 

When reviewing your results, we examine them in conjunction with everything we learned in our initial assessment. Next, we’ll meet with you to explain your combined risk (based on your PRS and other risk factors) and help you create a personalized prevention plan. As needed, we refer patients to medical specialists, dieticians, and lifestyle coaches. We also help coordinate additional screenings and medication plans. During the first year, we’ll check in multiple times to see how you are and where you might need additional support. From there, we provide long-term monitoring and support. Through annual follow-up assessments, we re-evaluate your risk and track the changes you’ve made in your life.

If you’re interested in getting PRS, fill out our contact form or call us directly at 303-832-7109.