Polygenic Scores Explained

Genetic Variation

Everyone has a genetic code that they inherit from each of their parents. Each person’s genetic code is made up of units of information, that contain instructions the body needs in order to function.

Most of the genetic code is identical between individuals. However, differences in the genetic code are called genetic variants.

Genetic variants contribute to traits that make us unique such as eye color, height, and taste preferences.

Genetic variants can also impact our risk of developing certain diseases — these are called risk variants.

Risk Variants

To discover risk variants, scientists compare the genetic codes of people without a disease to people with a disease.

If a genetic variant occurs more frequently in people with a disease, it is associated with increased risk.

If a genetic variant occurs more frequently in people without a disease, it is associated with decreased risk.

Risk variants can increase or decrease a person’s risk of disease and each can have different magnitudes of impact.

Some risk variants have a large impact on risk and some risk variants have a small impact on risk.

← small impact large impact →

A single, small impact variant has little impact on risk, but many of them together have a larger impact.

Polygenic Score Calculation

To calculate a person's polygenic score for a particular disease, scientists add up the total number of risk-increasing and risk-decreasing variants, along with their magnitude of impact.

A polygenic score tells you how your risk for disease compares to others.

Scientists can determine polygenic scores for a whole population.

Some people will have a higher or lower score, depending on their number of risk-increasing or risk-decreasing variants, and the magnitude of impact of each variant.

People with an approximately even number of risk-increasing and risk-decreasing variants are at an average risk of disease based on their genetics.

People with more risk-increasing variants are at an increased risk of disease based on their genetics.

People with more risk-decreasing variants are at a decreased risk of disease based on their genetics.

Polygenic Score Interpretation

Most people have average genetic risk of disease.

Your score can be higher than average meaning that you have increased genetic risk of disease compared to most people.

If your polygenic score is in the 95th percentile, you do not have a 95% chance of developing the disease. Rather it means that — out of 100 people — your polygenic score is higher than 95 people and the same or lower than 5.

Your score can be lower than average meaning that you have decreased genetic risk of disease compared to most people.

If your polygenic score is in the 5th percentile, you do not have a 5% chance of developing the disease. Rather it means that — out of 100 people — your polygenic score is higher than 5 people and the same or lower than 95.

Polygenic Score Application

Polygenic scores may be useful tools to assess risk for important diseases, such as coronary artery disease — a leading cause of death in the U.S. and globally.

Coronary artery disease occurs due to buildup of plaque in the blood vessels that supply oxygen-rich blood to the heart muscle. Starting as early as our 20's, plaques build up over time and ultimately increase risk of a totally clogged vessel, referred to as a myocardial infarction or 'heart attack.' In the U.S., about 5% (1 in 20) of individuals develop CAD by age 50, and up to 25% (1 in 4) develop CAD by age 80.

blood vessel

buildup of plaque

DNA is not destiny — additional factors influence your risk

A polygenic score for coronary artery disease is based only on the genetic code you were born with.

Even though you can’t change your polygenic score, following a healthy lifestyle and working with your health care team to treat any clinical risk factors can significantly decrease your risk.

The American Heart Association has outlined seven key factors that contribute to ideal cardiovascular health (‘Life’s Simple 7’). Individuals with at least five of these healthy factors have a 78% reduced risk for heart-related death compared to people without any healthy factors.

‘Life’s Simple 7’ factors include:

Manage Blood Pressure

A normal blood pressure is systolic (‘top number’) less than 120 mm Hg and diastolic (‘bottom number’) less than 80 mm Hg.

As compared to those with increased blood pressure, individuals with a normal blood pressure have a 24% lower risk* of coronary artery disease.

Control Cholesterol

A normal untreated total cholesterol for adults is <200 mg/dl. As compared to those with elevated cholesterol, individuals with normal cholesterol have a 16% lower risk* of coronary artery disease.

Reduce Blood Sugar

A normal blood sugar (‘fasting blood glucose’) is <100 mg/dl. As compared to those with elevated blood sugar, individuals with normal blood sugar have a 31% lower risk* of coronary artery disease.

Exercise Regularly

Current recommendations for physical activity suggest at least 150 minutes/week of moderate intensity exercise or 75 minutes/week of vigorous intensity exercise or combination.

As compared to those who do not exercise this amount, individuals who follow this recommendation have a 16% lower risk* of coronary artery disease.

Follow a Healthy Diet

A healthy diet is high in heart-healthy foods — fruits, vegetables, fish, whole grains — and low in unhealthy foods — sodium and sugar sweetened beverages.

As compared to those with an unhealthy diet pattern, individuals who follow a healthy diet have 27% lower risk* of coronary artery disease.

Maintain Normal Weight

A normal weight is defined as a body mass index less than 25 kg/m2. As compared to those with increased body mass index, individuals with a normal weight have 36% lower risk* of coronary artery disease.

Stop Smoking

Smoking is a leading preventable cause of coronary artery disease. As compared to those who have smoked, individuals who have never smoked have a 26% lower risk* of coronary artery disease.

UK Biobank