General PD Overview

  • GeneReviews: Overview of Parkinson’s Disease

    Cook Shukla L, Schulze J, Farlow J, et al. Parkinson Disease Overview. 2004 May 25 [Updated 2019 Jul 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.

    Informative review of the genetics of Parkinson’s disease including an evaluation strategy to identify the genetic cause of Parkinson’s disease in a patient and information for family members including genetic counseling.

  • Parkinson’s Disease

    Bloem, B. R., Okun, M. S. & Klein, C. Parkinson’s disease. Lancet 397, 2284–2303 (2021)

    A review of the complexities and challenges of PD including clinical features, risk factors, pathology, genetics, pathogenesis, diagnosis, and treatment.

  • NIH Genetics Home Reference: Parkinson’s Disease

    Kalia LV and Lang AE. Lancet 2015; 386(9996):896-912 DOI: 10.1016/S0140-6736(14)61393-3

    Overview of the clinical characteristics of PD along with the frequency, causes, and inheritance of PD.

PD Genetics

  • Genetic Forms of Parkinson’s Disease

    Kim C and Alcalay R. Genetic Forms of Parkinson’s Disease. Seminars in Neurology 2017; 37:135-146 DOI: 10.1055/s-0037-1601567

    A review of the key clinical features of the monogenic forms of PD including LRRK2, GBA, SNCA, VPS35, PRKN, PINK1, and DJ1. Information on phenotype, clinical course, and treatment response is included.

  • The Genetic Architecture of Parkinson’s Disease

    Blauwendraat C, Nalls MA, and Singleton AB. The Lancet Neurology, 2020; 19(2), 170–178 DOI: 10.1016/S1474-4422(19)30287-X

    The current knowledge of PD genetics, along with the most recent developments, are reviewed.

  • Clinical Genome Resource (ClinGen)

    View the PD gene-disease validity classifications approved by the ClinGen Parkinson’s Disease working group and gene curation panel.

  • Movement Disorder Society Genetic Database (MDSGene)

    Comprehensive overview of clinical data from patients with PD reported to carry causative variants

Genetic Testing for PD

  • The Role of Genetic Testing for Parkinson’s Disease

    Cook L, Schulze J, Naito A, Alcalay RN. Current Neurology and Neuroscience Reports, 2021, 8;21(4)17. DOI: 10.1007/s11910-021-01100-7 . (also provides downloadable patient flier about genetic testing)

    Provides guidance on facilitating PD genetic testing in a clinical practice given the changing scene of genetic testing for PD. Also highlights the current practices and attitudes among neurologists regarding genetic testing for PD.

    *Provides downloadable patient flier about genetic testing

  • Genetic Testing for Parkinson Disease: Are We Ready?

    Cook L, Schulze J, et al. Genetic Testing for Parkinson Disease: Are We Ready? Neurology: Clinical Pratice March 2020 DOI: 10.1212/CPJ.0000000000000831

    A review on the current genetic landscape of PD. Describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician.

  • Podcast: Are we ready for gene testing in Parkinson’s?

    Dr. Roy Alcalay and Lola Cook Neurology® Journals Podcast, March 15, 2021

    Dr. Jeffrey Ratliff talks with genetic counselor, Lola Cook, and neurologist, Dr. Roy Alcalay, about genetic testing for PD.

Risk Assessment

Parkinson’s disease (PD) is typically multifactorial, and many of the gene variants have incomplete penetrance and variable expression.

Guidelines for Medical and family history intake

Intake should include specific clinical information on both the patient and key relatives including:

  • age of onset and/or diagnosis

  • related neurologic or neurodegenerative conditions

  • prior genetic testing for the patient or family members

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 considerations during PD risk assessment

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

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.

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.