Genetics account for around 10% of Parkinson’s cases.
Genes can increase the risk of developing Parkinson’s, but having a mutation does not guarantee that you or your children will develop Parkinson’s.
How much do genes play a role in Parkinson’s?
Genes linked to Parkinson’s
Several genes have been definitively linked to Parkinson’s:
- SNCA makes the protein alpha-synuclein. It was the first gene identified to be associated with Parkinson’s. Research findings by the National Institutes of Health (NIH) and other institutions prompted studies of the role of alpha-synuclein in Parkinson’s. This led to the discovery that Lewy bodies seen in all cases of Parkinson’s contain clumps of abnormal alpha-synuclein. This discovery revealed the link between hereditary and sporadic forms of the condition.
- LRRK2 codes for a complex protein called dardarin that plays a role in many cellular functions. Research has shown that LRRK2 mutations affect how cells metabolise alpha-synuclein. These changes may lead to the formation of Lewy bodies. Studies suggest that the activity of this protein may increase in sporadic Parkinson’s.
- DJ-1 helps protect cells from oxidative stress, and mutations in this gene can cause rare, young onset forms of Parkinson’s.
- PRKN (Parkin) makes a protein that helps cells break down and recycle proteins. Mutations in this gene can cause young onset Parkinson’s.
- PINK1 codes for a protein active in mitochondria. Mutations in this gene appear to increase susceptibility to cellular stress. PINK1 has been linked to young onset forms of Parkinson’s.
- GBA (glucocerebrosidase-beta) mutations cause Gaucher disease. Different changes in this gene are associated with an increased risk for Parkinson’s and faster progression of symptoms in people who have Parkinson’s.
Genes such as SNCA, PARK2, PINK1, and LRRK2 can increase the risk of developing Parkinson’s, but they account for only 10-15% of all cases. It’s important to remember that having these genetic mutations does not guarantee that you or your children will develop Parkinson’s (i.e. about 90% of cases are not directly inherited). The collective influence of genes, environment, and lifestyle determines the likelihood of developing the condition, giving you some control over your health.
The role of genes in Parkinson’s
Genes play a significant role in Parkinson’s, influencing both the risk of developing the condition and its progression. Genetic mutations or variants in specific genes can increase the likelihood of developing PD, although most people with PD do not have a known genetic link.
Genetic risk refers to the likelihood of developing a disease based on one’s genetic makeup. In Parkinson’s, certain genetic mutations can increase the risk of developing the disease. These mutations can be inherited from parents or occur spontaneously. Understanding genetic risk helps researchers develop targeted treatments and personalised medicine strategies. If you are diagnosed with a genetic mutation in relation to Parkinson’s it is highly recommended to get genetic counselling to understand what this means for you and your relations.
The risk of passing Parkinson’s to children depends on the specific genetic mutations involved. If a parent has a genetic mutation linked to Parkinson’s, there is a chance their children may inherit it. However, most cases are due to a complex interplay of genetic and environmental factors, so having a genetic mutation does not guarantee that someone will develop the condition.
Factors contributing to genetic mutations
Several factors can contribute to genetic mutations, including:
- Inherited genetic mutations that are passed down from parents.
- Spontaneous mutations can occur randomly in the DNA.
- Environmental factors like exposure to toxins, pesticides, and other environmental factors can increase the risk of genetic mutations.
How do I access genetic testing in Australia?
In Australia, there are several options for genetic testing for Parkinson’s:
- Australian Parkinson’s Genetics Study (APGS) run by the QIMR Berghofer Medical Research Institute in Brisbane, aims to identify genetic factors influencing the risk of developing Parkinson’s disease. Participants can complete an online questionnaire and donate a saliva sample from home.
- Shake It Up Australia Foundation supports research into Parkinson’s disease, including genetic studies. They often collaborate with other research institutions to provide genetic testing and participate in studies like the APGS.
- Some specialist neurology clinics and hospitals in Australia may offer genetic testing as part of their diagnostic services. It’s best to consult with your neurologist or GP to get a referral to a specialist who can provide this testing.
- Occasionally, research studies and clinical trials may offer genetic testing as part of their recruitment process. Keep an eye on announcements from research institutions and foundations.
If you’re interested in participating in genetic testing, it’s a good idea to discuss it with your healthcare provider, who can guide you on the best options available based on your specific situation.
Known genetic mutations and their roles in disease risk
Here are some of the known genetic mutations associated with Parkinson’s disease and their roles in disease risk:
| Gene | Role in Disease Risk |
|---|---|
| SNCA | Produces alpha-synuclein protein, which forms Lewy bodies in brain cells. Mutations can cause early-onset PD. |
| PRKN | Produces parkin protein, involved in protein degradation. Mutations are a common cause of YOPD. |
| PINK1 | Produces a kinase that protects mitochondria. Mutations can cause YOPD. |
| LRRK2 | Produces a kinase involved in cell signaling. Mutations are linked to late-onset PD. |
| GBA | Produces glucocerebrosidase enzyme. Mutations are the most common genetic cause of PD. |
| PARK7 | Produces DJ-1 protein, which protects against mitochondrial stress. Mutations can cause YOPD. |
| VPS35 | Involved in vesicle trafficking. Mutations are a newly identified cause of PD. |
Infosheet under review
References
https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease
- Aasly, J. O. (2020). Long-term outcomes of genetic Parkinson’s disease. Journal of Movement Disorders, 13(2), 81–96. https://doi.org/10.14802/jmd.19080
- Day, J. O., & Mullin, S. (2021). The genetics of Parkinson’s disease and implications for clinical practice. Genes, 12(7), 1006. https://doi.org/10.3390/genes12071006
- Gunasekaran, A., Holla, V. V., Phulpagar, P., Kamath, S. D., Kamble, N., Yadav, R., Muthusamy, B., & Pal, P. K. (2024). Clinico-genetic profiles of seven patients with PINK1-related Parkinson’s disease: A case series from a tertiary care centre in India and a review of the literature. Journal of Movement Disorders, 17(4), 436–441. https://doi.org/10.14802/jmd.24157
- Klein, C., & Westenberger, A. (2012). Genetics of Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2(1), a008888. https://doi.org/10.1101/cshperspect.a008888
- Lange, L. M., & Klein, C. (2024). PINK1 type of young-onset Parkinson disease. In M. P. Adam, S. Bick, & G. M. Mirzaa (Eds.), GeneReviews®. University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK26472/
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