Abstract Details

Title Frequency of Known Genetic Variants for Parkinson’s Disease in the PD GENEration Study Cohort

Topic Movement Disorders

Presentation(s) S42 - Movement Disorders: Genetics and Risk Modifiers (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Background While precision medicine trials for PD have started, widespread access to clinical genetic testing and counseling for a large North American PD cohort has been limited.

Objective Assess the prevalence of pathogenic variants among people with Parkinson’s disease (PWP) through the PD GENEration study’s 7-gene genetic testing panel (LRRK2, GBA, SNCA, PRKN, PINK1, PARK7 and VPS35) and determine predictors of pathogenic variants.

Design/Methods This multi-center observational study provides genetic counseling and CLIA-certified genetic testing for PWP in the U.S., Canada and the Dominican Republic. DNA samples (buccal swab or blood) undergo next generation sequencing including deletion/duplication analyses. Pathogenic (P), likely pathogenic (LP) and select risk allele (RA) variants based on the American College of Medical Genetics (ACMG) classification criteria are returned to participants.

Results Over 5,500 participants have enrolled in the study between September 5, 2019 and October 1, 2022. Of the 4,080 completed tests, 563 individuals (13.8%) carried a reportable variant (P, LP, RA). The distribution of positive cases include: 338 GBA, 106 LRRK2, 94 PRKN, 6 VPS35, 9 SNCA, 5 PINK1, 5 PARK7, including 22 (0.54%) participants carrying variants in more than one gene. 1,860 out of 4,080 participants were viewed as having a higher genetic risk due to ancestry, positive first-degree family history, or age of onset <50; of those, 385, or 20.7%, were found to have a disease-related genetic variant. Of the other 2,220 participants with none of the above risk factors, 178, or 8.0%, had an abnormal genetic result.

Conclusions Genetic testing of well-established PD genes in this North American cohort resulted in a genetic diagnostic yield of 13.8%. Although reportable variants were more likely to be found in individuals who had early-onset PD, high-risk ancestry or a positive family history, a yield of approximately 8.0% was observed in those without these features.

Authors/Disclosures
James Beck, PhD (Parkinson'S Foundation) PRESENTER	Dr. Beck has received personal compensation for serving as an employee of Parkinson.
	No disclosure on file
Martha A. Nance, MD (Park Nicollet Clinic)	Dr. Nance has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Voyager. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROche. Dr. Nance has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. An immediate family member of Dr. Nance has received stock or an ownership interest from Fresca. The institution of Dr. Nance has received research support from HDSA. The institution of Dr. Nance has received research support from Parkinson Foundation. Dr. Nance has received research support from Parkinson Foundation. The institution of Dr. Nance has received research support from Neuraly. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving as a speaker with AAN.
	No disclosure on file
Niccolo Mencacci, MD, PhD (Northwestern University)	The institution of Dr. Mencacci has received research support from Parkinson's foundation.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Anne Marie A. Wills, MD (MGH)	Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant, a CVS/Caremark company. Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi/Genzyme. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharmaceuticals. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Wills has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson's Foundation. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylyx Pharmaceuticals. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharmaceuticals. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Wills has received research support from Parkinson's Foundation. The institution of Dr. Wills has received research support from Biogen. The institution of Dr. Wills has received research support from Roche/Genentech. The institution of Dr. Wills has received research support from BioSensics.
Michael Schwarzschild, MD, PhD (Massachusetts General Hospital)	The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson's Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities.
Karen S. Marder, MD, MPH, FAAN (Columbia University)	Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Marder has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson's Foundation . Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CHDI. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer LTD. The institution of Dr. Marder has received research support from Vaccinex. The institution of Dr. Marder has received research support from Genentech. The institution of Dr. Marder has received research support from Triplet Therapeutics. The institution of Dr. Marder has received research support from Prilenia.
Tanya Simuni, MD, FAAN (Northwestern University Feinberg School of Medicien)	Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for cadia, AcureX, Adamas, AskBio, Amneal, Blue Rock Therapeutics, Caraway Therapeutics, Critical Path for Parkinson's Consortium (CPP), Denali, Michael J Fox Foundation, Neuroderm, Sanofi, Sinopia, Roche, Takeda and Vanqua Bio. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for of Koneksa, Neuroderm, Sanofi, UCB, AcureX, Adamas, AskBio, Biohaven, Denali, GAIN, Neuron23 and Roche. Dr. Simuni has received research support from Amneal, Biogen, Neuroderm, Prevail, Roche, and UCB and an investigator for NINDS, MJFF, Parkinson's Foundation.
	No disclosure on file
Jennifer Verbrugge (Indiana University School of Medicine)	Jennifer Verbrugge has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Tatiana Foroud, PhD (Indiana University School of Medicine)	The institution of Dr. Foroud has received research support from NIH. The institution of Dr. Foroud has received research support from Michael J. Fox Foundation. The institution of Dr. Foroud has received research support from Parkinson Foundation. Dr. Foroud has received personal compensation in the range of $500-$4,999 for serving as a Member of an Advisory Committee with Mayo Clinic, University of Pennsylvania, Allen Institute, Mt. Sinai, Van Andel Institute.
Roy Alcalay, MD (Columbia University)	Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.