Clinical Domain Working Groups

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1 million Americans. There is an urgent need for expert consensus on determining the causal genes and variants for PD due to the rise in both the availability of genetic testing, as well as precision medicine clinical trials that are actively seeking candidates with genetic forms of PD.

In this context, the Parkinson’s Foundation (a nonprofit PD patient and research advocacy organization) launched the PD GENEration study (NCT04057794), which offers CLIA-accredited testing and genetic counseling to people with PD. As part of this study, and to meet the broader needs of the research community, we have already convened an international multidisciplinary expert panel of molecular geneticists, clinicians with genetic research focus, and PD-specific genetic counselors to assess gene- disease validity for an initial set of seven PD genes (LRRK2, GBA, PRKN, PINK1, SNCA, PARK7 and VPS35) using ClinGen’s framework. 

The scope of work for the GCEP will encompass 21 genes. While LRRK2, GBA, PRKN, PINK1, SNCA, PARK7 and VPS35 have a reasonable consensus as to the causality for PD and will be the initial focus, we further plan to address 14 genes recently published by panel members, Blauwendraat and Singleton (PMID: 31521533). Importantly, we will focus our efforts on developing consensus on genes with low confidence that have been cited in the literature and/or included on commercially available genetic testing panels (e.g., Athena Diagnostics, Invitae, Prevention Genetics, and others).