Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar 13;149(1):60-71.
doi: 10.1093/bmb/ldad035.

Genetics in Parkinson's disease, state-of-the-art and future perspectives

L Trevisan  1   2 , A Gaudio  3 , E Monfrini  4   5 , L Avanzino  6   7 , A Di Fonzo  4   5 , P Mandich  1   3
Affiliations
Review

Genetics in Parkinson's disease, state-of-the-art and future perspectives

L Trevisan et al. Br Med Bull. .

Abstract

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is clinically characterized by the presence of motor (bradykinesia, rigidity, rest tremor and postural instability) and non-motor symptoms (cognitive impairment, autonomic dysfunction, sleep disorders, depression and hyposmia). The aetiology of PD is unknown except for a small but significant contribution of monogenic forms.

Sources of data: No new data were generated or analyzed in support of this review.

Areas of agreement: Up to 15% of PD patients carry pathogenic variants in PD-associated genes. Some of these genes are associated with mendelian inheritance, while others act as risk factors. Genetic background influences age of onset, disease course, prognosis and therapeutic response.

Areas of controversy: Genetic testing is not routinely offered in the clinical setting, but it may have relevant implications, especially in terms of prognosis, response to therapies and inclusion in clinical trials. Widely adopted clinical guidelines on genetic testing are still lacking and open to debate. Some new genetic associations are still awaiting confirmation, and selecting the appropriate genes to be included in diagnostic panels represents a difficult task. Finally, it is still under study whether (and to which degree) specific genetic forms may influence the outcome of PD therapies.

Growing points: Polygenic Risk Scores (PRS) may represent a useful tool to genetically stratify the population in terms of disease risk, prognosis and therapeutic outcomes.

Areas timely for developing research: The application of PRS and integrated multi-omics in PD promises to improve the personalized care of patients.

Keywords: Parkinson’s disease; Polygenic Risk Scores; genetics; tailored therapies.

PubMed Disclaimer

Conflict of interest statement

The authors have no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of the pathways involved in the pathogenesis of Parkinson’s disease. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA 2020;323:548–60. 10.1001/jama.2019.22360. - DOI - PubMed
    1. Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–4. 10.1136/jnnp.55.3.181. - DOI - PMC - PubMed
    1. Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson’s disease: diagnosis and management. The Lancet Neurology 2006;5:235–45. 10.1016/S1474-4422(06)70373-8. - DOI - PubMed
    1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30:1591–601. 10.1002/mds.26424. - DOI - PubMed
    1. Isaacson SH, Fisher S, Gupta F, et al. Clinical utility of DaTscan™ imaging in the evaluation of patients with parkinsonism: a US perspective. Expert Rev Neurother 2017;17:219–25. 10.1080/14737175.2017.1256205. - DOI - PubMed

Publication types