Parkinson’s Genes Explained: 5 Facts about LRRK2

Genes are the instructions for making the proteins that give us individual characteristics. Just as genes influence traits like eye color or height, sometimes there are changes to a person’s genes — called genetic variants or mutations — that increase the risk of developing certain diseases.

In some people, Parkinson’s disease (PD) can be linked to genetic factors. The PD GENEration: Powered by the Parkinson’s Foundation genetics study found that about 1 in 8 participants has a genetic variant related to Parkinson’s. 

This blog outlines five facts about one of the genes examined in PD GENEration, LRRK2, and why studying it is important for the entire Parkinson’s community. 

The Genetics of LRRK2 

LRRK2 (pronounced “Lark Two”) stands for Leucine-rich repeat kinase 2 and was discovered in 2002. Since then, studies have shown that variations in this gene are related to developing Parkinson’s disease. 

Everyone inherits two copies of the LRRK2 gene — one from each parent. Changes in LRRK2 follow a dominant inheritance pattern, meaning a variant in just one copy of the gene can increase a person’s risk for Parkinson’s disease. 

However, these variants also have “reduced penetrance,” which means that the gene doesn’t act alone to cause Parkinson’s. Whether someone with a LRRK2 variant eventually develops Parkinson’s depends on a combination of genetics and other factors like age and environment. Some people carry a LRRK2 variant but never show symptoms of PD.

1. LRRK2 variants are a common genetic contributor to developing late-onset Parkinson’s. 

PD GENEration, the international research study providing genetic testing and counseling at no cost for people with PD, looks for changes in several Parkinson’s-related genes including LRRK2. To date, PD GENEration has found that:

• 12% of participants have a variant in one or more of the genes tested.
• About 2% of participants have a LRRK2 variant.

Most PD (with or without a variant) is considered late-onset, starting later in life and involving changes like slowed movement and shaking.

The way Parkinson’s appears in people with a LRRK2 variant does not look physically different than Parkinson’s in people without this change. Because of the similarities, researchers are investigating whether understanding LRRK2 could open doors to new treatments for all people with Parkinson’s. 

2. Certain ethnic groups are more likely to have LRRK2 variants. 

Different ancestral and ethnic groups can have different risks for genetic diseases. Findings from PD GENEration show that 10.5% of people who identify as Ashkenazi Jewish, 4.0% of people who identify as Berber, and 3.8% of people who identify as Basque carried a LRRK2 variant — compared to 1.2% of people who identified as having none of these ancestries.

People with a higher chance of having a LRRK2 variant can use genetic testing like PD GENEration to better understand their genetic makeup for themselves and their families. 

“For me, it was reassuring to learn that I am a LRRK2 carrier, because then I knew that we had a target. There are clinical studies I can participate in to help advance the field. Within a week of learning that I have a genetic variant, I was participating in research, and I’ve been participating in research ever since.”

-Jessi Keavney, Parkinson’s Foundation Research Advocate

3. A variant in the LRRK2 gene may make it harder for cells to clear out unwanted material. 

The LRRK2 gene gives cells instructions to make the LRRK2 protein, which is responsible for powering the cell and directing nutrients and waste. A variant in LRRK2 can make the protein too active, disrupting the way a cell’s materials are normally transported. 

Research suggests that while LRRK2 normally helps cells clean up and recycle waste, LRRK2 variants may stop this system from working properly. Waste can collect in cells — including in brain cells called neurons. When this happens, the buildup can lead to inflammation and cell death. Early Parkinson’s symptoms appear after the loss of neurons that make dopamine, a chemical that helps the body coordinate movement.

4. LRRK2 is a target for new PD treatments. 

Scientists are highly focused on how mutations in the LRRK2 gene influence Parkinson’s disease. By developing treatments to calm or quiet an overactive LRRK2 gene, researchers hope to protect brain cells and potentially slow or halt the progression of Parkinson’s. 

There are several active clinical trials — studies that test new treatments — for therapies targeting LRRK2 in Parkinson’s. Some studies require a confirmed LRRK2 variant, which can be verified with clinical-grade genetic testing like PD GENEration.   

For those who have already participated in PD GENEration, our PD Trial Navigator program currently partners with Neuron23 for the Neulark trial for LRRK2. For more information about Neulark or other partner trials as they become available, email PDNavigator@parkinson.org. 

5. LRRK2 breakthroughs could benefit the entire PD community. 

Even highly targeted genetic research has the potential to help broader communities. For example, research into a rare genetic condition called familial hypercholesterolemia (FH) helped scientists discover how the body regulates cholesterol. This led to the creation of statins, a medication that lowers cholesterol and is widely used today by people with and without FH.

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Scientists are hoping LRRK2 research may hold broader promise because of the similarities between LRRK2-related Parkinson’s and the more common idiopathic Parkinson’s — PD without a known cause. What they discover could help many people with Parkinson's in the future. 

Learn More  

The Parkinson’s Foundation works to improve care for people with PD and advance research toward a cure. Learn more with these resources: 

• Learn about and enroll in PD GENEration to find out if you have a LRRK2 or another Parkinson’s-related gene variant. 
• Learn more about our PD Trial Navigator program and the Neulark study, email PDNavigator@Parkinson.org. 
• Explore ways to get involved in the Parkinson’s Foundation, like becoming a Research Advocate or by sharing your Parkinson’s story.