Risk Assessment

Parkinson’s disease (PD) is typically multifactorial, and many of the gene variants have incomplete penetrance and variable expression. Medical and family history intake should include specific clinical information on both the patient and key relatives.

This includes:

  • age of onset and/or diagnosis

  • related conditions

  • prior genetic testing

Early deaths, adoptions, and small family structures should be documented as this can result in under ascertainment of cases when doing risk assessment.

Ethnicity of the family on both maternal and paternal sides should be noted, including Ashkenazi Jewish ancestry.

Below are important factors to consider when considering PD genetic risk.

Key factors to consider during PD risk assessment

Baseline risk in general population

  • 3-4% lifetime risk in general population (GeneReviews)

  • Overall, idiopathic PD is more common in males.

  • Late-onset PD is considered to be multifactorial in most cases.

Age of onset

  • Early-onset PD (EOPD, or YOPD; when diagnosed <50 years old) is more likely to be genetic, and more likely to follow autosomal recessive inheritance.

  • With increasing age, the risk of PD increases.

Family history

  • 10-15% of PD is familial.

  • The lifetime risk of PD increases to 6-8% if an individual has a family member with PD; however, with a family history suggesting autosomal dominant or autosomal recessive inheritance, the individual’s lifetime risk can be even higher than that (based on discovered or undiscovered genes).

  • Relevant family history can include PD or related conditions (essential tremor, parkinsonism, dementia with Lewy bodies [LBD], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], multiple system atrophy [MSA]), or Gaucher disease.

  • Individuals without a family history have been reported to have a genetic variant.

  • Reduced penetrance & variable expressivity in PD genetics can affect risk assessment.

Ancestry

  • Any ancestry can have a genetic variant.

  • Ancestry impacts risk of developing PD, depending on the variant.

  • Founder variants are known in Ashkenazi Jewish (GBA, LRRK2), North African Berber and Spanish Basque (LRRK2), and Europeans (GBA, other).

Patient or relative with a KNOWN family variant

Patient had previous NEGATIVE results

  • More comprehensive testing may be available if the testing was limited to DTC, single-gene, multi-site, or research only. DTC/research testing may only include specific variants, and some commercial panel testing may not include all genes or variants relevant to PD.

  • A negative genetic test result does not entirely rule out a genetic contribution to disease.

*adapted from NSGC Neurogenetics Special Interest Group (SIG) Movement Disorder Working Group Parkinson’s disease Resource Toolkit

For information on specific gene and variant risk-associations please view our Parkinson's Disease Gene Penetrance resource.

Click here for additional references and articles on the genetics of Parkinson’s disease

Educational Factsheets for Patients & Participants

The team at Indiana University and PDNexus have developed a series of patient education factsheets for use in clinic and research, which are available to print or download.

Articles and Key Resources

Updates and overviews on the genetics of Parkinson’s disease, current testing options, and tips for patient discussion are available through several resources: