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TOPLINE: 

Genetic variants associated with Parkinson's disease (PD) are more common than previously thought and occur in 13% of individuals with the disease. The study highlights the importance of genetic testing and counseling for those with PD.

METHODOLOGY: 

• Participants were part of PD GENEration, a multicenter, observational registry, and clinical study offering genetic testing and genetic counseling to people with PD in North America, with an original enrollment goal of 15,000 by 2025.
• Following participant consent and sample collection, testing of the genes LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7, and VPS35 was performed using next-generation sequencing and data analysis on genomic DNA.
• Variants were classified into five-tier categories: Pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign.

TAKEAWAY:

• To date, more than 10,510 people with PD across North America have enrolled in the study, with 8301 having completed genetic testing.
• Reportable variants were found in 1070 (12.9%) of the 8301 participants. GBA1 variants were the most frequently identified, followed by LRRK2 and PRKN (7.7%, 2.4%, and 2.1%, respectively).
• Participants with GBA1 variants or presumed compound heterozygous or homozygous PRKN variants had an earlier age at onset (AAO) than those with negative results (58.6 and 38.6 vs 61.5 years).
• The carriers of SNCA variants had an earlier AAO than those with negative results (49.2 vs 61.5 years), though the numbers were too small for statistical comparison.
• The positivity rate of a genetic variant was significantly higher for individuals with elevated risk, investigators reported. Those with an early AAO; high-risk ancestry including as Ashkenazi Jewish, Spanish Basque, or North African Berber; or a first-degree relative affected with the disease had an 18% positivity rate.

IN PRACTICE: 

"We did not anticipate the high positivity rate for genetic mutations, specifically the nearly 10% having a positive result even without any known genetic risk factors," Roy Alcalay said in a press release. "Further, the speed at which participants enrolled in PD GENEration is a testament to the interest of people with PD to obtain data on their genetic status," Alcalay added.

SOURCE: 

Roy Alcalay, MD, MS, Tel Aviv Medical Center, Tel Aviv, Israel, and the Department of Neurology, Columbia University Irving Medical Center, New York City, led the study, which was published online on July 30 in Brain. 

LIMITATIONS: 

Despite early efforts, one study limitation was its relative lack of racial and ethnic diversity. Therefore, the results may not be directly applicable to non-European populations. Additionally, self-enrollment and physician recruitment may have biased the study toward participants with an early AAO, a positive family history, or a high-risk ancestry, resulting in some degree of enrichment.

DISCLOSURES: 

The study was funded by the Parkinson's Foundation and the National Institute on Aging. Alcalay reported receiving grants from the Parkinson's Foundation for acting as a steering committee member, funding from the National Institutes of Health, The Michael J. Fox Foundation, and the Silverstein Foundation for Parkinson's with GBA. He received consulting fees from Biogen, Biohaven, Capsida, Gain Therapeutics, Sanofi, Servier, Takeda, Vanqua Bio, and the Department of Defense. Other disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.