Genetic variants that increase the risk of Parkinson’s disease

Parkinson’s disease is a neurological disorder caused by the degradation of dopamine-producing neurons in a part of the brain called the substantia nigra. It affects up to 10 million people worldwide. Symptoms of Parkinson’s include a tremor (usually in the hand), problems with balance and walking, problems with moving limbs, and, for some, depression, sleep problems, and dementia. Loss of the sense of smell is often an early symptom that may happen several years before any of the motor symptoms.[ref]

This article covers some of the genetic variants that increase the risk of Parkinson’s disease as well as links with environmental and lifestyle factors.

Is Parkinson’s Disease Hereditary?

Parkinson’s disease (PD) is not yet fully understood. Researchers think it is caused by a combo of genetics and environmental factors.

For early-onset Parkinson’s, several genetic mutations are thought to cause it, but this type of PD only affects about 10% of patients.

For late-onset Parkinson’s disease, it is likely a combination of genetic variants that increase susceptibility combined with specific environmental causes.

Environmental Causes

Environmental causes of PD (that probably combine with genetic susceptibility) include exposure to certain toxins.[ref]

Paraquat is a herbicide that has been linked to increasing the risk for PD.[ref] It is still in use in the US, but the EU banned it in 2007. Maneb is a fungicide also linked to PD. It is often used to create Parkinson’s in animal research. Mancozeb is another formulation of maneb, and it is sold under a variety of brand names and is used for potato blight, downy mildew on grapes, and other plant fungal diseases.

Trichloroethylene (aka trichlor) is another chemical that is linked to PD.[ref] It is an industrial solvent and is used in refrigerants. Initially, trichloroethylene was used as an anesthetic as an alternative to ether and chloroform. But better anesthetics have come along, and trichloroethylene had a nasty side effect of cardiac arrhythmia and neurologic dysfunction. The EPA now lists it as having both carcinogenic and non-carcinogenic health effects. The main route of exposure is contaminated drinking water in areas near industrial spills or landfill leaks.

Twin studies help researchers determine whether a disease is genetic or caused by an environmental factor. The risk of solvent exposure was made clear in a study of 97 twin pairs where one twin had PD, and the other didn’t. Exposure to trichloroethylene increased the risk of PD by 6-fold, and combined exposure to perchloroethylene and carbon tetrachloride was also found to significantly increase the risk of PD.[ref]

Genetic Risk Factors for Parkinson’s Disease:

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These genetic variants do not cause Parkinson’s on their own. Rather, exposure to environmental factors along with genetic susceptibility is thought to lead to PD.
LRRK2 gene:
Mutations in this gene are linked to a higher risk of Parkinson’s disease. There are rare mutations that lead to early-onset disease. Of the LRRK2 variants listed below, the G2019S variant listed first causes the most significant increase in risk, and it may be one that you should talk to your doctor about getting a second genetic test to confirm.

Check your genetic data for rs34637584 G2019S (23andMe v4, v5):

  • G/G: typical
  • A/G: significantly increased risk of Parkinson’s[ref]
  • A/A: significantly increased risk of Parkinson’s[ref]

Note: This genetic variant may be misreported on AncestryDNA version 2 data.

Members: Your genotype for rs34637584 is .

Check your genetic data for rs34778348 G2385R (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • A/G: increased risk of Parkinson’s
  • A/A: increased risk of Parkinson’s[ref][ref]

Members: Your genotype for rs34778348 is .

Check your genetic data for rs33995883 N2081D ( 23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: increased risk of Crohn’s disease, slight increased risk for Parkinson’s depending on the study[ref][ref]
  • G/G: increased risk of Crohn’s disease, slight increased risk for Parkinson’s depending on the study[ref][ref]

Members: Your genotype for rs33995883 is .

SNCA gene: alpha-synuclein is found in the terminal of neurons.

Check your genetic data for rs2736990 (23andMe v4, v5; AncestryDNA)

  • A/A: typical risk of Parkinson’s
  • A/G: slightly increased risk of Parkinson’s (really common variant)
  • G/G: increased risk for Parkinson’s[ref]

Members: Your genotype for rs2736990 is .

Check your genetic data for rs356218 (AncestryDNA only):

  • A/A: typical risk of Parkinson’s
  • A/G: slight increased risk of Parkinson’s (really common variant)
  • G/G: slight increased risk of Parkinson’s[ref]

Members: Your genotype for rs356218 is .

PER1 gene: A circadian clock gene.

Check your genetic data for rs2253820 (23andMe v4 only; AncestryDNA):

  • T/T: typical risk of Parkinson’s
  • C/T: slight increased risk of Parkinson’s
  • C/C: slight increased risk of Parkinson’s[ref]

Members: Your genotype for rs2253820 is .

SLC2A13 gene: Facilitated glucose transport gene.

Check your genetic data for rs1994090 (23andMe v4, v5; AncestryDNA):

  • G/G: increased risk of Parkinson’s disease[ref]
  • G/T: slightly increased risk of Parkinson’s disease
  • T/T: typical

Members: Your genotype for rs1994090 is .

ALDH gene: Aldehyde dehydrogenase gene

Check your genetic data for rs671 ( 23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • A/G: increased risk of PD with pesticide exposure, inc. dementia
  • A/A: increased risk of PD with pesticide exposure, inc. dementia[ref][ref][ref]

Members: Your genotype for rs671 is .

Gaucher’s disease and Parkinson’s:

Gaucher’s disease is a genetic liposomal storage disease. Most people with the disease carry two copies of a mutated GBA gene. The GBA gene codes for an enzyme called β-Glucocerebrosidase, which is part of the lysosome. People with Gaucher’s disease are at an increased risk for Parkinson’s disease — and people who carry one mutation are also at an increased risk for Parkinson’s disease. A study published in the Journal of the American Medical Association found that almost 10% of the 500+ Parkinson’s patients investigated carried a mutation for Gaucher’s disease, compared with 0.3% of the control group without Parkinson’s. This mutation leads to a 28-fold increase in the risk for Parkinson’s.[ref]

Check your genetic data for rs421016 L444P (23andMe v4):

  • A/A: typical
  • A/G: increased risk for Parkinson’s
  • G/G: increased risk for Parkinson’s and Gaucher’s disease[ref][ref]

Members: Your genotype for rs421016 is .

Check your genetic data for rs387906315 ( 23andMe i4000417 v4, v5):

  • DD (or –): typical
  • DI (or -C): increased risk for Parkinson’s (carrier for Goucher’s)
  • II (or C/C): increased risk for Parkinson’s and Goucher’s disease.[ref]

Members: Your genotype for i4000417 is .

Check your genetic data for rs2230288 (23andMe v4, v5):

  • C/C: typical
  • C/T: increased risk for PD
  • T/T: 2x increased risk for PD, Goucher’s[ref]

Members: Your genotype for rs2230288 is .

Lifehacks for Preventing Parkinson’s:

First, let me make it clear that you should always talk with your doctor if you suspect you are in the early stages of Parkinson’s disease. Health care providers can prescribe many medications to delay the progression of the disease. The lifehacks listed here are things to consider – along with whatever treatment course you’ve decided on with your doctor.

Get Your Circadian Rhythm In Sync:

This article on the circadian disruption in Parkinson’s explains that dopamine plays a vital role in circadian rhythms. Parkinson’s disease patients are likely to exhibit quite a few circadian rhythm disorder symptoms, including sleep disorders, body temperature decreases, and autonomic system disruptions such as blood pressure disturbances.

Here is another good review of circadian disruption in Parkinson’s disease. The thought is that while circadian disruption doesn’t cause Parkinson’s, the disturbance to the dopaminergic neurons possibly causes the circadian disruption, which then may exacerbate or add to the neurodegenerative process.[ref]

So if the circadian rhythm dysfunction is integral to PD, it makes sense to do everything you can to keep your circadian rhythm in sync. This includes:

  • regular sleep/wake schedule,
  • sunlight during the day to stop melatonin during the day,
  • blocking blue light at night to increase melatonin,
  • eating on a regular schedule (not too late at night).

Let me further explain the reason for blocking blue light at night:
Light in the blue wavelengths (~480nm) signals through photoreceptors in the retina that it is daytime. It blocks melatonin production and resets your circadian rhythm for the day. Beyond melatonin, there is a circadian rhythm to dopamine as its levels rise and fall over the course of a day. Mouse studies are showing that constant light disrupts the rhythm of dopamine production.[ref]


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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.