Genetics is the single biggest predictor of an individual’s risk for many common diseases.
Every person has a different risk profile for disease. That profile is made up of different risk factors – things that increase your chances of developing a particular disease. Those risk factors can include things such as age, biological sex, weight, or family history. If you are overweight, your risk for diabetes and cardiovascular is elevated. As you age, your risk of developing most forms of cancer increases across the board.
Some risk factors are changeable, by behaviour (such as giving up smoking) or medication (such as lowering cholesterol levels). Others can’t be changed – like age, biological sex, or your genetics.
Your doctor anticipates illness by measuring those risk factors, and then choosing the levers that can be pulled to bring the changeable risk factors downwards. That lever might be a change in medication, a change in behaviour, or a change to the frequency or type of screening you get, so that if you do get sick your doctor picks it up early.
An individual’s unique genetic make-up is a risk factor for nearly all types of disease. For some diseases – like Huntington’s or cystic fibrosis – genetics is all of the story. If you have a certain genetic mutation you are very likely, or even assured, to get that illness. But for most diseases, including common diseases such as heart disease or prostate cancer, there isn’t a single gene that drives the disease. Instead, the way your genetics influences your likelihood of developing disease is spread across tens of thousands of sites across the genome, which are inconsequential on their own – but summed correctly, can detect significant levels of risk.
Those sums are Polygenic Risk Scores: a way to measure the genetic risk factor for a common disease. Individuals who have a high Polygenic Risk Score for a particular disease have much higher incidences of that disease – sometimes, their risk for a particular disease is the same as someone 10-15 years older than them. For many common diseases, Polygenic Risk Scores are the single most powerful element that you can measure. For breast cancer, they are even more predictive than knowing about other risk factors such as your family history, your BMI, whether you have had hormone replacement therapy, or whether you’ve gone through the menopause. For coronary artery disease too, Polygenic Risk Scores are comparable in their predictive power to key measurements used by your doctor, such as your total cholesterol levels.
The greatest power of a Polygenic Risk Score comes when we integrate it with all of the other risk factors known to play a part in disease risk, to form what is commonly known as an Integrated Risk Tool. These tools can fit seamlessly into doctors’ existing practices. For instance, doctors in the UK measure risk for heart disease using a clinical risk score called QRISK (and in the US, PCE). These combine factors such as age, sex, BMI, smoking history, cholesterol level, blood pressure, and family history, and the results help doctors decide whether or not to assign a patient blood-pressure-lowering medication such as statins. Adding a Polygenic Risk Score into those calculations substantially improves them.
What does this all mean? It means that for many common diseases, doctors have the opportunity to give risk-appropriate advice and medication, including preventative treatment. It means screening can be organised and targeted according to those most at risk. And it means that we can take something that is largely unchangeable – your genetics – and turn it into an incredibly powerful tool for you to manage your health.