• L Trevisan, A Gaudio, E Monfrini, L Avanzino, A Di Fonzo, and P Mandich.
• Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Largo P. Daneo 3, Genova, 16132, Italy.
• Br. Med. Bull. 2024 Mar 13; 149 (1): 607160-71.

BackgroundParkinson'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 DataNo new data were generated or analyzed in support of this review.Areas Of AgreementUp 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 ControversyGenetic 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 PointsPolygenic 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 ResearchThe application of PRS and integrated multi-omics in PD promises to improve the personalized care of patients.© The Author(s) 2024. Published by Oxford University Press.

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