Approved Research

Parkinson's disease risk and phenoconversion: a polygenic risk score approach

Lay summary

Parkinson's disease (PD) is the second most common neurodegenerative disease in older adults. PD is expected to become more common as the population gets older. There is a set of conditions that commonly develop (sometimes >10 years) before movement related symptoms occur and PD can be diagnosed. This period is called the PD prodrome.

Cardiometabolic health is a term that refers to the health of a person's heart, blood, and blood vessels. It also is related to how a person's body can turn food components like sugar and fat into energy. Health conditions like heart disease, diabetes, obesity, or high blood pressure are called cardiometabolic diseases. Some studies have suggested that people with these conditions have a higher risk of PD. However, the results from studies so far have not been the same. Sometimes in studies where participants are not randomized (like the flip of a coin) to a study treatment, there can be bias. The bias could have played a role in the different conclusions. We want to reduce these biases by studying genetic factors that are related to a person's risk for diabetes or high blood pressure. Genetic factors do not change over a person's lifetime. There are many of these genetic factors that play a role in a person's risk for diabetes or high blood pressure. Together, they are called 'diabetes genetic scores' or 'high blood pressure genetic scores.' The goal of this study is to see if these genetic scores can predict PD risk. There are also genetic scores that can affect how well diabetes medicines or high blood pressure medicines work. Sometimes the genetic factors can make the medicines work better. We also want to see if the genetic factors making the medicines work better can predict less PD. We will see if these genetic factors can impact how fast someone with PD prodromal symptoms develops diagnosable PD. We will use genetic factors for many kinds of diabetes or high blood pressure medicines. We expect to find that there are genetic factors for one type of medicine that can predict less disability. If so, then future studies could test if taking the medicine itself can prevent PD or developing PD fully in people at high risk. Since all these medicines are already available and can be prescribed by doctors today, the results could open the doors for many new potential medicines to prevent PD.