By Matthew J. Kmiecik, Ph.D.
April is Parkinson’s Awareness Month, a time dedicated to increasing education about the condition and highlighting the incredible progress being made in research. At the 23andMe Research Institute, this month holds a special significance. Since 2009, we have been committed to uncovering the genetic underpinnings of Parkinson’s disease to help pave the way for future breakthroughs.
Understanding Parkinson’s Disease
Parkinson’s disease is a neurodegenerative condition characterized by tremors, muscle stiffness, and challenges with movement and balance. Motor symptoms can be just the tip of the iceberg, as many non-motor symptoms also occur, including sleep disturbances, loss of smell, and constipation. While it typically develops after the age of 55, the journey for every individual is unique.
About 1–2% of people develop Parkinson’s during their lifetime. While we are still learning why some people develop the condition and others don’t, we know that a combination of factors is at play:
- Age: Risk increases as we get older.
- Sex: Males have a higher likelihood of developing Parkinson’s than females.
- Environment: Exposure to certain chemicals, such as pesticides and chemicals used for metal degreasing or dry cleaning, can increase risk.
- Family History: Having a first-degree relative (parents, siblings, and children) with the condition can increase your own chances.
- Head Injury: Some studies suggest that head injury, in particular those that result in prolonged loss of consciousness, can increase the risk of developing Parkinson’s disease later in life.
The Genetic Connection
For some people, DNA plays an important role in their chances of developing Parkinson’s. Two of the most well-studied genes associated with Parkinson’s are LRRK2 and GBA (also known as GBA1). 23andMe offers the Parkinson’s Disease Genetic Health Risk report* that specifically looks at two genetic variants: one in each of these genes associated with an increased risk of developing Parkinson’s disease. The chance that someone carrying these variants actually develops Parkinson’s is different depending on what variant they carry. Estimates range from roughly 24% to over 50% for LRRK2 G2019S carriers[1][2], and from about 10% to 30% for GBA1 N409S carriers (formerly known as N370S)[3][4], depending on the study and genetic ancestry.
What Our Research Adds
While most people who have these variants will not develop Parkinson’s, recent research from the 23andMe Research Institute and collaborators has helped us better understand the nuances of the condition and why it affects every individual differently.
- The researchers found that a person’s overall genetic background can “dial” their risk up or down. Among GBA1 carriers, those with a low-risk genetic background had roughly the same chance of developing Parkinson’s as non-carriers. But GBA1 carriers with a high-risk genetic background were about five times more likely to develop the disease. The takeaway: carrying one variant is only part of the picture, as many other genes and variants across the genome can nudge the risk up or down.
- For carriers of both LRRK2 and GBA1 carriers, the risk was even higher. This research showed that these “dual carriers” face a much higher risk of developing Parkinson’s—about a 30% chance by the age of 80, compared to just 2% in people without either genetic variant.
- Genetics don’t just influence whether someone develops Parkinson’s; it also impacts how the disease progresses. The researchers found that in those already living with PD, carrying APOE e4—commonly associated with Alzheimer’s disease—increases the risk of experiencing hallucinations, memory challenges, and concentration issues. In fact, each additional copy of the APOE e4 raised the risk of these symptoms by 11% to 35%.
Power in Numbers: 17 Years of Research
Since launching our Parkinson’s research community in 2009, the 23andMe Research Institute has grown one of the largest genetic studies of Parkinson’s disease in the world. Our study has included more than 30,000 consented research participants with Parkinson’s. Their ongoing contribution has led to more than 30 publications on Parkinson’s disease, most recently a paper exploring other biological factors that might influence Parkinson’s disease risk or progression.
This progress is only possible because of this community who make up one of the world’s largest genetic studies of Parkinson’s disease. A large study size is what allows scientists to zoom in on tiny DNA clues that would be impossible to spot in just a small handful of people.
How You Can Get Involved
Awareness is the first step toward action. This Parkinson’s Awareness Month you can:
- Share the facts about PD symptoms and risks with your loved ones.
- If you are a 23andMe member, you can opt-in and view your Parkinson’s Disease Genetic Health Risk report.
- If you or a loved one are living with Parkinson’s or you’re just interested in this research, consider joining our research community.
This April, consider taking a step toward greater awareness for yourself, and for the millions of people living with Parkinson’s disease around the world.
About the Author
Matthew J. Kmiecik, Ph.D. — Scientist I, Parkinson’s Disease Research
Dr. Matthew Kmiecik is a cognitive neuroscientist whose research has long focused on how the brain processes information under conditions of injury and disease. With over a decade of research experience, Dr. Kmiecik is a Scientist at the 23andMe Research Institute, where his work is supported by The Michael J. Fox Foundation for Parkinson’s Research. His current research focuses on identifying genetic and biological markers of Parkinson’s disease risk and progression, including cognitive assessments, sensory measurements, and wearable-based tools to better understand how the disease unfolds over time.
* The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. The test is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment. The Parkinson’s Disease genetic health risk report is indicated for reporting of the G2019S variant in the LRRK2 gene, and the N409S variant (formerly known as N370S) in the GBA gene and describes if a person has variants associated with an increased risk of developing Parkinson’s disease. The variants included in this report are most common and best studied in people of European, Ashkenazi Jewish, and North African Berber descent.
References
[1] Clark, L. N., Wang, Y., Karlins, E., Saito, L., Mejia-Santana, H., Harris, J., Louis, E. D., Cote, L. J., Andrews, H., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R., & Marder, K. (2006). Frequency of LRRK2 mutations in early- and late-onset Parkinson disease. Neurology, 67(10), 1786–1791. https://doi.org/10.1212/01.wnl.0000244345.49809.36
[2] Kmiecik, M. J., Micheletti, S., Coker, D., Heilbron, K., Shi, J., Stagaman, K., Filshtein Sonmez, T., Fontanillas, P., Shringarpure, S., Wetzel, M., Rowbotham, H. M., Cannon, P., Shelton, J. F., Hinds, D. A., Tung, J. Y., 23andMe Research Team, Holmes, M. V., Aslibekyan, S., & Norcliffe-Kaufmann, L. (2024). Genetic analysis and natural history of Parkinson’s disease due to the LRRK2 G2019S variant. Brain, 147(6), 1996–2008. https://doi.org/10.1093/brain/awae073
[3] Rana, H. Q., Balwani, M., Bier, L., & Alcalay, R. N. (2013). Age-specific Parkinson disease risk in GBA mutation carriers: Information for genetic counseling. Genetics in Medicine, 15(2), 146–149. https://doi.org/10.1038/gim.2012.107
[4] Anheim, M., Elbaz, A., Lesage, S., Durr, A., Condroyer, C., Viallet, F., Pollak, P., Bonaïti, B., Bonaïti-Pellié, C., & Brice, A. (2012). Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers. Neurology, 78(6), 417–420. https://doi.org/10.1212/WNL.0b013e318245f476
