Understanding Genetics

People with Parkinson's disease (PD) experience major differences in their symptoms, responses to medications and side effects of treatments. Understanding genetic differences across people with Parkinson's can help researchers uncover important clues about how and why each person's experience with PD differs.

Genetics is the field of science that examines how traits are passed down, or inherited, from parents to children through genes. Genetics has transformed our knowledge of PD and paved the way for many innovations in treatment.

Understanding DNA

The study of genetics begins with our DNA. All living things have DNA inside the cells that make up the tissues of their bodies. DNA is made of molecules organized into strands in specific orders that can be read like letters in a book.

The full sequence of DNA contains three billion of these letters, which are organized into individual genes, just as letters form words and sentences.

Like a recipe in a cookbook, a gene is a section of DNA that tells the body how to make a certain protein. Proteins play many critical roles in the body and are required for the structure, function and regulation of the body’s tissues and organs. There are more than 24,000 genes written in our DNA, and each gene can be thought of like a recipe or an instruction manual that the cells of the body reads and interprets to build the protein.

Genetic Variants

A change in a gene’ s DNA, known as a variant, can alter the instructions for making a protein. In some cases, this may result in changes to a protein’s shape or normal function.

Variants in our genes are mostly harmless, but in some cases, they can cause the differences we see in hair color, skin color, height, behavior and risk of getting a disease. Understanding these changes in genes associated with PD is the basis for our genetics study, PD GENEration, which aims to determine the genetic makeup of people with Parkinson's in the U.S and across the world.

Variants can also be referred to as “mutations,” as the two terms are sometimes used interchangeably. The word mutation is best to describe a genetic variant that is known to directly cause a disease. Because some genetic variants related to PD are only risk factors and there are other non-genetic factors that can contribute to PD, we use the term genetic variant to describe changes in the DNA that might contribute to Parkinson’s.

A person who has a genetic variant in their DNA can be referred to as a variant carrier. In addition to genetics, environmental factors and lifestyle choices strongly determine if a person will develop Parkinson's.

Understanding the role of genes in PD can help pave the way to understanding the biological causes of disease and developing new therapies to treat or cure Parkinson's. These gene variants change the role a protein plays and influences the risk for developing Parkinson's.

Not all people with gene variants develop Parkinson's and by understanding different inherited genetic backgrounds of people with Parkinson's, we can begin to understand what causes some people to develop certain symptoms while others do not.

Inheritance Patterns

Genetic variants can be inherited from a person’s parents. We all have two copies of every gene — one copy of DNA passed down from our biological mother and one copy of DNA passed down from our biological father.

Depending on the gene associated with Parkinson’s, a person may only need one copy of their gene to have a variant to contribute to PD risk or both copies of the gene may need to have a variant to contribute to PD risk. This is referred to as a gene’s inheritance pattern.

If a disease, like PD, is caused by only one copy of a gene having a genetic variant, the inheritance pattern is called dominant.

If a disease is only caused when both copies of someone’s gene have genetic variants, the inheritance pattern is called recessive.

There are also genes that are considered risk factors for a disease, meaning that carrying a variant in the gene does not cause the disease with absolute certainty. Instead, these risk factor variants only increase the likelihood of someone getting a disease compared to someone who does not have a particular risk factor variant.  Many people who are carriers of risk factor variants may never get Parkinson’s.

Parkinson’s-Related Genes

One major challenge in treating Parkinson's is that no one can predict how the disease will manifest in different people. No two people with PD experience the exact same symptoms, age of onset, rate of progression and even treatment response. Genetics may help explain some of these differences.

Scientists have identified variants in several genes associated with Parkinson's. However, some of these gene changes or variants seem to be more common than others among people with PD.

The genes listed below are among the most common that have been found to have genetic variants in people with PD. Variants in these genes cause the protein that is made from the gene’s instructions to not function properly or at all.  The changes in these genes have been shown to increase the risk of developing Parkinson's.

Seven genes associated with Parkinson's include:  

• GBA: The most common Parkinson’s-related gene. A risk factor gene accounting for 7.6% of PD GENEration participants. People with PD that have a variant in GBA may experience PD symptoms at an earlier age compared to people who don’t have a genetic form of PD. Learn more about GBA.

• LRRK2: Plays a role in about 5% of those with a family history of Parkinson’s. The gene has a dominant inheritance pattern, and variant carriers have been reported to have milder symptoms of dementia and depression. Learn more about LRRK2.

• PRKN: The most common gene with variants associated with recessive young-onset Parkinson’s, which appears before age 50. Carriers may be more likely to experience early symptoms, such as bradykinesia (slowness of movement) and rigidity, and respond well to the PD medication levodopa. Learn more about PRKN.

• SNCA: The first PD-related gene to be identified, commonly associated with dominant young-onset Parkinson’s. Carriers usually have a parent with Parkinson’s. In the PD GENEration study, only 0.1% of people with PD have been found to have a variant in SNCA. Learn more about SNCA.

• PINK1: The second most common gene with variants associated with recessive young-onset Parkinson’s. Carriers generally experience slow disease progression and respond well to the PD medication levodopa. Learn more about PINK1.

• PARK7: Variants in this gene are associated with recessive young-onset Parkinson’s and lead to a decrease in a protein called DJ-1 that is essential for nerve cell health. Learn more about PARK7.

• VPS35: Only discovered in 2011, variants in this gene are rare and were recently associated with dominantly inherited Parkinson’s. Learn more about VPS35.

Genetic Research

Genetic research has made great strides to help scientists better understand the biology of Parkinson's and guide the development of treatments for all people with PD. The Parkinson’s Foundation genetic study, PD GENEration: Mapping the Future of Parkinson’s Disease, provides genetic testing and genetic counseling at no cost to people with Parkinson’s.

The study’s comprehensive genetic test identifies variants in all of the Parkinson’s-related genes listed above, as well as some rarer gene variants associated with PD.

Identifying whether you carry a genetic variant can help you better manage your disease alongside your care team and determine if you are eligible to enroll in genetics-related clinical trials.