Genetic results from people with PD tested through PD GENEration show that approximately 13% of people with Parkinson’s have a genetic variant (a change in their DNA) that contributes to their disease. These variants are found in multiple genes known to play a role in Parkinson’s.
Participating in PD GENEration empowers you and your care team with your genetic data. Further, the genetic data contributes to research to better understand how those with genetic forms of PD experience symptoms and respond to treatment. This information helps scientists and medical professionals develop improved treatments and personalized medicine strategies that treat PD.
>20,000
enrolled globally in PD GENEration
~13%
genetic positivity in PD risk genes
More than 20,000 people with PD have enrolled in the PD GENEration study, including participants from the U.S. and Canada, Chile, Colombia, the Dominican Republic, Ecuador, Israel, Mexico and Peru.
We are committed to expanding to new countries and aim to increase the racial diversity of study participants. This is crucial for improvements in the understanding and treatment of PD across the globe.
What genes does PD GENEration test?
PD GENEration uses a comprehensive genetic test to detect changes (known as variants) in genes associated with Parkinson’s. For an overview of the PD GENEration testing panel, watch this informational video.
The PD GENEration test identifies genetic changes in seven Parkinson’s-related genes: GBA, LRRK2, PRKN, SNCA, PINK1, PARK7 and VPS35. In addition — if the person with PD chooses — the test can report genetic changes in other PD-related genes and certain non-PD related genes that are related to diseases that can be prevented or treated, called the CDC-10, Tier 1 genes.
Primary Parkinson’s Disease Genes
GBA (or GBA1) is the most common Parkinson’s-related gene, with variantsfound in 5-10% of people with PD. In contrast to the other six genes tested through PD GENEration, variants within GBA are consideredrisk factors of PD, as they only increase the likelihood of someone developing PD.
Many carriers of a GBA variant will never develop PD, even if they have a family member with PD who carries the same GBA variant. Other risk factors, such as age and environment, may beneeded for an individual to develop PD in addition to carrying a GBA variant.
While carrying a single heterozygousGBA variant in one of your two copies of the gene is enough to increase the risk of developing PD, having two variants in the gene — a homozygous variant seen in both copies of GBA — further increases the risk for developing PD, and in some cases, causes Gaucher’s disease.
Those who carry a GBA variant may experience:
PD symptoms at an earlier age
More rapid progression of dementia symptoms
Greater motor difficulties compared to people who don’t have a genetic form of PD
Ongoing Research
Researchers are exploring exactly how GBA variants increase PD risk in brain cells. One theory suggests that the protein produced by the GBA gene, which has a role in the cell's garbage disposal system and is called GCase (glucocerebrosidase), may not work properly due to a variant in the gene. This would lead to the build-up of toxic clumps of the protein alpha-synuclein, which is known to happen in the brain of people with PD.
Pharmaceutical companies are testing drugs that target GBA to help slow or stop the progression of Parkinson's, and the clinical trials will enroll people with PD that carry variants in this gene.
Variantsin the LRRK2 gene are found in about 1% of all people with PD and 5% of those with a family history. Certain ethnic groups have higher prevalence of LRRK2 variants among people with PD, like Ashkenazi Jews (about 15%) and North African Berbers (about 40%).
Although variants in LRRK2 are largely considered causative of PD, there are some people who carry variants in the gene that never develop PD. The risk of developing PD increases with age and varies depending on the specific LRRK2 variant a person has.
LRRK2 has a dominant inheritance pattern for PD (a person only needs to have a single heterozygous variant in one copy of the gene to cause the disease).
People with PD with a LRRK2 variant often experience:
Symptoms similar to those with a form of PD with an unknown cause
On average, milder symptoms of dementia and depression
Less frequent motor difficulties
Slower progression
Symptoms vary from person-to-person, and researchers are still working to better understand why
Ongoing Research
Researchers are studying the mechanisms of how LRRK2 variants lead to Parkinson’s. Evidence suggests a change in the protein function from variants in the gene. One theory is that LRRK2 variants can increase the frequency at which the encoded protein triggers specific pathways that lead to cell death, particularly in dopaminergic neurons, which is a known cause of PD.
LRRK2 variants may also interfere with a cell waste disposal method (called autophagy) that may lead to the buildup of a toxic protein called alpha-synuclein found in the brains of people with PD.
Pharmaceutical companies are testing drugs that block the abnormal activity of this gene to treat Parkinson's, and the clinical trials will enroll people with PD that carry variants in LRRK2.
Learn More
ExploreGeneReviewsfor additional information about the symptoms and genetic counselling of LRRK2 PD.
Genetic variantsin PRKN are the most common cause of young-onset Parkinson’s, which appears before age 50. Although rarer than GBA or LRRK2, variants in PRKN are more common in certain ethnic groups, such as a group from Malaysia with a high rate of young-onset PD, of whom more than 50% have variants in PRKN.
More than 200 PRKN gene variants have been identified that are related to PD.
PRKN displays a recessive inheritance pattern (the person with PD must have a homozygous variant in both copies of the gene to cause the disease). Although, researchers are questioning whether people with PD with only a single PRKN variant may also have an increased risk of the disease.
The PRKN gene provides instructions for making a protein called parkin in cells. Studies have found some of the variants in PRKN lead to a defective version of parkin or prevent the production of the protein. A loss of parkin may affect the production of dopamine. In people with Parkinson’s, the brain gradually stops making dopamine leading to abnormal movements and balance problems. Variants in the PRKN gene may also disrupt the proper disposal of damaged mitochondria (the powerhouse of the cell). Some research suggests that this dysregulation could play a key role in causing Parkinson’s symptoms.
Pharmaceutical companies are studying treatments that could boost or repair parkin protein activity.
Learn More
ExploreGeneReviewsforadditional details regarding the symptoms and genetic counselling of PRKN PD.
SNCA was the first Parkinson’s-related gene to be identified. In 1997, Parkinson's Foundation research fellow Roger Duvoisin, MD, identified the geneas playing a role in developing PD. There are at least 30 variantsin the SNCA gene that can alter the SNCA protein, although they are considered a relatively rare cause of PD in comparison to genes such as LRRK2 and GBA.
Disease-causing variants in SNCA display a dominant inheritance pattern (the person with PD only needs to have a variant on one copy of their two SNCA genes to cause disease).
People with a SNCA variant:
Usually have a parent with Parkinson’s, from which they inherited the variant
May progress more rapidly than people with PD without a genetic cause
Can experience early non-movement symptoms, such as cognitive decline
Ongoing Research
SNCA produces the protein alpha-synuclein. When there is too much of this protein it can clump into deposits called Lewy bodies in neuron cells and contribute to their death. These clumps are seen even in people with PD that do not have a SNCA variant and are considered potential causes of Parkinson’s symptoms and/or Lewy body dementia.
Researchers have found that SNCA variants can lead to the accumulation of Lewy bodies by two different mechanisms:
The variants cause the alpha-synuclein protein to not fold properly and clump together, or
The variants result in an overproduction of alpha-synuclein that cannot be destroyed quickly enough and the proteins clump together.
Researchers are studying the SNCA gene to design treatments that can reduce levels of toxic alpha-synuclein clumps in people with Parkinson's.
PINK1 is the second most common cause of young-onset Parkinson’s. There are more than 70 variantsin the PINK1 gene that can cause Parkinson’s.
PINK1 displays a recessive inheritance pattern (the disease being caused when the person with PD has a homozygous variant, meaning a variant in both copies of their PINK1 gene). Yet, researchers have also found that people with PD with only a single PINK1 heterozygous variant may have an increased risk of the disease.
PINK1 Parkinson’s and PRKN Parkinson’s have some similarities. PINK1 carriers often experience:
Early symptoms such as bradykinesia and rigidity
Less common non-movement symptoms, such as dementia
Generally slow disease progression
Good response to the PD medication levodopa
Ongoing Research
PINK1 provides the instructions for the cell to make a specific kinase protein (proteins that activate or inactivate other proteins), which has roles in similar cell pathways as the parkin protein produced from PRKN. The variants within PINK1 seem to cause a loss of the protein’s function, resulting in decreased dopamine production and selective death of neuron cells, which can contribute to the loss of movement control. Variants in PINK1 may also be involved in disrupting the regulation of mitochondria (the powerhouse of the cell).
Researchers are working to understand the role of these gene variants in mitochondrial dysfunction, and how it may lead to PD.
Pharmaceutical companies are studying treatments that could boost PINK1 protein activators to help clear out mitochondria and keep cells healthy.
Learn More
ExploreGeneReviewsfor additional details regarding the symptoms and genetic counselling of PINK1 PD.
Variantsin PARK7, also referred to as DJ-1, are a rare cause of young-onset Parkinson’s, accounting for 1-2%of people that are diagnosed with PD before age 50. Even rarer, variants in the gene have been found to cause juvenile-onset Parkinson’s (under 21 years of age) as well as late-onset Parkinson’s (after 50 years of age).
PARK7 displays a recessive inheritance pattern (the person with PD must have a homozygous variant, in both copies of their gene, to cause the disease).
People with PD that have variants in PARK7:
Typically have similar experiences to people with non-genetic Parkinson’s
Often respond well to levodopa medication
Ongoing Research
The protein encoded by PARK7 is called DJ-1, and variants within the gene typically cause there to be a decrease in the amount of functional protein produced. Under normal circumstances, DJ-1 helps protect from a destructive process called oxidative stress that damages dopamine-producing neuron cells. But PARK7 variants impair the protein’s ability to protect the cell, resulting in a large reduction in dopamine neurons, known to result in abnormal movements and balance problems in people with PD.
Current studies are looking to better understand how the reduction in DJ-1 triggers the death of nerve cells that produce dopamine. Researchers are studying whether treatments focused on DJ-1 could delay nerve cell death.
Discovered in 2011, variantsin VPS35 are considered a relatively rare cause of late-onset of Parkinson’s, which begins after age 50. Although different variants have been reported in the gene in people with PD, most research studies have found that the risk of Parkinson’s results from one specific variant within VPS35.
The gene displays a dominant inheritance pattern (people with PD only need one copy of their VPS35 gene to have a variant to cause Parkinson’s).
People with a VPS35 variant:
· Tend to have similar symptoms as people with non-genetic PD
· In some cases, may have milder PD and/or slower progression
Ongoing Research
VPS35 variants result in a dysfunctional protein that interrupts the brain’s Retromer system, which helps brain proteins communicate. Some researchers also think that the variants can result in reduced breakdown of alpha-synuclein, which may lead to it clumping into Lewy bodies in the brains of people with PD.
The Parkinson’s Foundation PD GENEration team is studying how variants in VPS35 contribute to the symptoms of PD. Understanding more about the gene can lead to the development of treatment strategies.
Learn More
ExploreGeneReviewsfor additional details regarding the symptoms and genetic counselling of VPS35 PD.
PD GENEration participants can choose to receive results that include DNA sequencing and variant assessment of additional genes that have been associated with PD or other Parkinson’s-related diseases beyond the seven genes listed above.
Secondary findings genes include genes that are either associated with rare types of PD or are genes that we are only beginning to find evidence of an association with Parkinson’s. We are still learning more about these genes through research.
ATP13A2: Associated with recessive, juvenile-onset Kufor-Rakeb syndrome, which has symptoms of parkinsonism and dementia. Researchers are also investigating whether the gene may be associated with risk of dominant late-onset PD.
ATP1A3: Associated with dominant, rapid-onset dystonia with parkinsonism symptoms.
ATP7B: Associated with recessive Wilson disease, which can sometimes have parkinsonism symptoms. Researchers are also investigating whether the gene is associated with risk of dominant early-onset PD.
CHCHD2: Research suggests a potential association with dominant, late-onset PD.
DCTN1: Associated with dominant, adult-onset Perry syndrome, which can have parkinsonism symptoms. Researchers are also investigating whether the gene may be associated with dominant progressive supranuclear palsy, which can sometimes have parkinsonism symptoms.
DNAJC6: Associated with recessive juvenile-onset and young-onset PD.
FBXO7: Associated with recessive, young-onset PD.
GCH1: Associated with dominant and recessive dystonia, which can have parkinsonism symptoms. Research also suggests that the gene may be associated with an increased risk of dominant PD without dystonia.
GRN: Associated with dominant and recessive frontotemporal dementia that sometimes has parkinsonism symptoms. Research also suggests that the gene could be associated with dominant Lewy body dementia, which is related to PD.
MAPT: Associated with dominant frontotemporal dementia that sometimes has parkinsonism symptoms. Research also suggests the gene may be associated with an increased risk of PD.
PLA2G6: Associated with recessive, late-onset PD.
POLG: Associated with dominant and recessive forms of progressive external ophthalmoplegia, which can have parkinsonism symptoms.
PTRHD1: Associated with recessive neurodevelopmental disorder with young-onset PD.
RAB32: New research suggests a potential association with increased risk of dominant, late-onset PD.
RAB39B: Associated with X-linked recessive Waisman syndrome with young-onset PD.
SLC6A3: Associated with recessive, infant-onset parkinsonism-dystonia.
SYNJ1: Associated with recessive, young-onset PD.
TBK1: New research suggests a potential association with parkinsonian-pyramidal syndrome, as well as a potential association with amyotrophic lateral sclerosis with symptoms of parkinsonism.
TH: Associated with recessive, infant onset Segawa syndrome with parkinsonism symptoms.
VCP1: New research suggests a potential association with PD, as well as a potential association with amyotrophic lateral sclerosis and/or frontotemporal dementia with symptoms of parkinsonism.
VPS13C: Associated with recessive, young-onset PD.
Non-PD Related CDC-10 Tier 1 Genes
PD GENEration participants can also choose to receive results from additional genes called the Centers for Disease Control and Prevention (CDC)-10 Tier 1 genes. This genetic testing is completed only if the PD GENEration participant agrees to it.
These 10 genes tested are not related to Parkinson’s disease but are known to cause other diseases that can be prevented or treated if the person with the variant knows they have a genetic risk.
Genes included in this test include:
Two genes, BRCA1 and BRCA2, associated with hereditary breast and ovarian cancer syndrome
Five genes, MLH1, MSH2, MSH6, PMS2 and EPCAM, associated with Lynch syndrome (or hereditary nonpolyposis colorectal cancer syndrome)
Three genes, LDLR, APOB and PCSK9, associated familial hypercholesterolemia (hereditary high cholesterol)
Learn More
Visit the CDC webpage to learn more about these 10 genes and how they were selected.
PD GENEration Results
PD GENEration results have found that approximately 13% of people with PD carry a genetic variant in one of the seven primary PD-related genes that is contributing to their Parkinson’s.
In 2024, the scientists and clinicians behind PD GENEration published the interim results of the study in a peer-reviewed journal, called Brain. These results not only updated the estimate of people who live with a genetic form of PD but also show the willingness of the PD community to learn their genetic risk of disease.
Enroll in Our Genetics Study
PD GENEration is a national initiative that offers genetic testing for Parkinson's-related genes and genetic counseling at no cost for people with Parkinson’s.
PD GENEration genetic test results are returned to participants through a genetic counseling appointment. If someone tests positive for a genetic variant related to Parkinson’s, the genetic counselor will discuss and interpret the genetic variant that was found, the gene it is in and answer any questions while providing emotional support.
If someone tests positive for a variant in a PD-related gene, their children may have a higher chance of developing PD if they inherit the genetic variant. However, there is still no guarantee they will develop Parkinson’s. Many people with these gene variants do not get PD.
The genetic counsellor can help navigate if and how someone might want to share genetic testing results with family members and the impact they could have.
The PD GENEration test is also not a substitute for a PD diagnosis. In other words, if someone tests negative with the genetic test and is not found to have a PD gene variant, it does not mean that they do not have Parkinson’s.
Most people with PD that enroll in PD GENEration will test negative for a PD gene variant. A person who tests negative may have experienced environmental factors that increased their risk of PD, or they may have a genetic variant in a PD-related gene that has not yet been discovered by researchers.
Parkinson's Disease Gene and Variant Curation Expert Panels
The NIH appointed the Parkinson’s Foundation to convene international multidisciplinary expert panels of the world’s most esteemed molecular geneticists, clinicians with a general research focus and PD-specific genetic counselors.
These groups of experts are known as the ClinGen PD Gene Curation Expert Panel (GCEP) and Variant Curation Expert Panel (VCEP). They aim to support the expansion of high-quality and expert-driven variant curation for PD-relevant genes such as LRRK2, GBA, SNCA, PRKN, PINK1, PARK7 and VPS35.