Parkinson's Disease and Genetic Testing - What You Need to Know
23andMe now provides FDA-approved reports on Parkinson's disease risk, and I thought readers could benefit from a post specific to the condition. This guest post was written by my friend and former colleague, Lola Cook Shukla, who specializes in the genetics of Parkinson's disease. Lola is a genetic counselor who provides telephone genetic counseling to participants who are part of a large Parkinson’s disease research study, sponsored by the Michael J. Fox Foundation. The wing of the study focused on Parkinson’s genetic testing is located at Indiana University School of Medicine.
Thank you, Lola, for sharing your expertise with us! There's a lot of nuance to the risk of developing Parkinson's, and I appreciate the chance you've given us to understand it better.
Parkinson’s Disease and Genetic Testing: What You Need to Know
by Lola Cook Shukla, MS, LGC
The company 23andMe began again to offer genetic testing for specific health risks in 2017, including Parkinson’s disease. Parkinson’s disease is a common adult-onset movement disorder. Genetic testing may tell you that you have an increased risk for developing Parkinson’s disease; however, it cannot tell you for sure if you will or will not get the disorder. In other words, regardless of your genetic test results, you may or may not develop Parkinson’s disease in your lifetime.
Here are some quick facts about Parkinson’s disease:
It is a chronic and progressive movement disorder.
About 1-2% of all people will develop Parkinson’s disease in their lifetimes.
The average age of onset for the most common type is age 60.
Dopamine deficiency causes Parkinson’s features which include slow movement, rigidity of the muscles, tremor, and gait problems.
Other features may include changes in the ability to smell, cognitive and psychiatric symptoms, sleep disorders, pain, and fatigue.
“Regardless of your genetic test results, you may or may not develop Parkinson’s disease.”
What Causes Parkinson’s Disease?
Factors observed to increase or decrease risk include:
Ethnicity
Family history of disease
Genetic risk factors
History of head trauma
Exposures to certain chemicals and infectious agents
Caffeine use
Exercise
Parkinson’s disease was previously thought to be caused mainly by environmental factors, but research now indicates that in most cases the disease develops from a complicated interplay of genetics and environment.
23andMe’s test screens for changes (variants) in two genes, LRRK2 and GBA. However, there are additional variants in LRRK2 and GBA, and other genes, that 23andMe doesn’t test for that are likely involved in the development of Parkinson’s. It is difficult to check for these other changes either because they are infrequent or have unclear significance. In addition, it becomes more expensive to test for more rare and subtle changes.
Some environmental factors that have been implicated include severe head trauma, chemical exposures such as pesticides, and infectious agents. There are also possible protective factors. Caffeine use and moderate to vigorous exercise might be protective, so drinking your coffee while briskly walking may be healthy steps you can take to keep Parkinson’s at bay!
“Caffeine use and moderate to vigorous exercise might be protective.”
Ethnicity and family history influence a person’s chances. Having Ashkenazi (Eastern European) Jewish background increases the chance of carrying a change in LRRK2 and GBA - so does having more than one relative in the family with the disorder.
It is reassuring to know that the majority of individuals with a genetic risk variant will never develop the disorder since LRRK2 and GBA variants need other factors to cause their expression. Keep in mind that regardless of a genetic result there remains a baseline risk of developing Parkinson’s for everyone. Although a risk may be provided by a genetic test report, this is only an estimate and does not take into account personal factors that could impact risk. Researchers are very interested in knowing why some people with these risk variants develop Parkinson disease, and others do not.
Implications of Test Results for Other Family
When individuals decide to have genetic testing for Parkinson’s disease, they may inadvertently learn that other relatives have a risk as well. For example, carrying a variant associated with PD often means one or the other parent has it as well. It could also mean children, siblings, aunts, uncles, and cousins may have the variant, too.
Not everyone wants to know if they carry a genetic risk for which there is no clear and effective treatment to slow or prevent the disease at this point in time. This genetic risk could be information that other family members may or may not want to know, which is something to consider if you test yourself. Genetic disorders in general are often a family affair with a family member’s risk rippling out to others. This can be seen as helpful news or unwelcome news from one person to the next.
“This genetic risk could be information that other family members may or may not want to know, which is something to consider if you test yourself.”
More About the GBA Gene and Gaucher Disease
Another interesting aspect of testing for Parkinson’s disease is that variants in the GBA gene are not just associated with Parkinson’s but also a very different disorder – Gaucher disease. Gaucher disease is a metabolic disorder often manifesting in childhood, which can vary in severity.
Possessing one or two copies of a GBA variant is a risk factor for Parkinson’s whereas carrying two GBA variants (the one you get from your father and the one you get from your mother) causes Gaucher disease. Persons who carry one GBA variant do not have Gaucher disease, but have the potential to have a child with Gaucher disease if two variants are passed on. This means that finding out if one carries a GBA mutation may also have implications for pregnancy and family planning.
23andMe reports on more GBA variants in your Gaucher disease report than they include on your Parkinson’s disease risk report at this point in time. This means your report - and therefore your understanding of your risk for PD - may change over time. If you’d want to know if you have an increased Parkinson’s disease risk, make sure to pay attention to update emails 23andMe sends you.
“Your [23andMe] report - and therefore your understanding of your risk for PD - may change over time.”
Why Do Healthy People Choose to Test for Parkinson’s Disease Risk?
Healthy individuals may decide to have genetic testing for Parkinson’s disease for multiple reasons:
It is part of the consumer testing like 23andMe that they are already doing
For information purposes for themselves or their family
To reduce anxiety about risk
Out of curiosity
To help in research studies
It is important to think carefully about the potential implications of testing before doing it. It may be beneficial to speak to a genetic counselor, a trained professional who helps individuals better understand the benefits and limitations of a particular genetic test, before and/or after testing.
What Can You Do?
Individuals who are interested in being part of a Parkinson’s disease research study may consider joining the Parkinson’s Progression Markers Initiative (PPMI). This study, offered through the Michael J. Fox Foundation, aims to identify biomarkers (physical indicators) of PD by enrolling individuals with a genetic predisposition to the disease into an observational research study. Typical requirements for the study include: Jewish heritage and having Parkinson’s disease or a first-degree relative with the disorder, or knowledge of carrying a LRRK2 or GBA change.
Other places to search for Parkinson’s research studies and clinical trials are www.clinicaltrials.gov or in the "Get Involved" tab on the Michael J. Fox Foundation’s website.
