A 500-genome pilot project in the Global Parkinson’s Genetics Program (GP2), an international effort created to help explore the connection between genetics and Parkinson disease (PD) was explained during a poster presentation at the 146^th Annual Meeting of the American Neurological Association.

“In spite of the most recent advances in sequencing and genotyping technologies, the vast majority of patients with Parkinson's disease, even when a monogenic cause is strongly suspected, for instance, based on the presence of a positive family history, or a very young onset of symptoms…even in these cases, a genetic etiology remains not detectable in a very significant proportion,” said Niccolo E. Mencacci, MD, PhD, Neurology, Northwestern University, Chicago, IL, USA.

Researchers have established a screening process and online case submission platform known as the Monogenic Hub, to allow them to perform whole-genome sequencing on 500 patients with PD within 279 families with suspected genetic causes in an effort to identify novel monogenic causes of PD.

A total of 16 research teams across 10 countries submitted 757 patients with PD into the hub. Important prioritization criteria included available samples from other effected family members, availability of previous genetic testing, age at onset with younger ages being prioritized, and ethnicity. A total of 504 cases were selected for the pilot project cohort, approximately 75% of the cases being familial with up to 9 affected members.

About 93% of the patients showed negative genetic pre-screening and about 20% were from underrepresented populations such as Southeast Asia and South America.

“The samples are currently being whole genome sequenced and we expect to start the analysis of the first 500 channels very soon,” Dr Mencacci said.

This pilot project is the first of what researchers hope will be a short or long-read whole-genome sequencing for up to 10,000 patients with PD.

“This study is anticipated to contribute to the identification of a novel monogenic causes of Parkinson's disease,” Dr Mencacci concluded.

—Erin McGuinness

Mencacci, N, Lange, L, et al. Monogenic Hub of the Global Parkinson’s Genetics Program (GP2): The 500 Genomes Pilot Project. Presented at: the Annual Meeting of the American Neurological Association; October 17-19, 2021; Virtual. Presentation: 397.