PD-Related Genes Contribute to Disease in 15% of Patients

Approximately 15% of patients with Parkinson disease (PD) in a large international cohort had potentially actionable genetic variants, according to a study published in the journal Brain.

The finding “offers an important prospect to affected individuals and their families,” researchers wrote, “and underlines the need for genetic testing in PD patients.”

With limited data on the spectrum and frequency of pathogenic variants in PD in different populations, the Rostock Parkinson’s disease (ROPAD) study investigated variants in 50 genes with either an established PD relevance or possible phenotypic overlap in 12,580 patients with PD from 16 countries.

Positive PD-relevant genetic test (PDGT) results occurred in 14.8% of participants, according to the study. The genetic contribution was conferred by GBA1 risk variants in 10.4% and pathogenic/likely pathogenic variants in LRRK2 in 2.9%, PRKN in 0.9%, SNCA in 0.2%, and PINK1 in 0.1%. A combination of two genetic findings in two genes occurred in approximately 0.2% of participants.

“∼90% of patients with a positive PDGT had variants in LRRK2 or GBA1,” researchers pointed out, “making these individuals potential candidates to be included in gene-targeted trials.”

Positive PDGT results occurred in 19.9% of patients who were younger than 50 years at the age of PD onset, 19.5% of patients with a positive family history, and 26.9% of patients with both factors, researchers reported. Overall, patients with positive PDGT had significantly lower age of onset compared with patients with idiopathic PD. With every additional year before onset, the probability of a positive PDGT decreased 3%. The study also found a 22% higher likelihood of a positive PDGT among female patients. Patients with a positive family history, meanwhile, had a 55% higher likelihood of a positive PDGT.

“[I]nsights from the ROPAD study allow for data-driven, differential genetic counseling across the spectrum of different ages of onsets and family histories,” researchers wrote, “and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.”

Reference

Westenberger A, Skrahina V, Usnich T, et al. Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson's disease study. Brain. 2024;147(8):2652-2667. doi: 10.1093/brain/awae188