Parkinson’s Disease Pathogenic Variants: Cross-Ancestry Analysis and Microarray Data Validation
Background
Known pathogenic variants in Parkinson’s disease (PD) contribute to disease development but
have yet to be fully explored by arrays at scale.
Objectives
This study evaluated genotyping success of the NeuroBooster array (NBA) and determined the
frequencies of pathogenic variants across ancestries.
Method
We analyzed the presence and allele frequency of 34 pathogenic variants in 28,710 PD cases,
9,614 other neurodegenerative disorder cases, and 15,821 controls across 11 ancestries within
the Global Parkinson’s Genetics Program dataset. Of these, 25 were genotyped on NBA and
cluster plots were used to assess their quality.
Results
Genes previously predicted to have high or very high confidence of causing PD tend to have
more pathogenic variants and are present across ancestry groups. Twenty-five of the 34
pathogenic variants were typed by the NBA array and classified “good” (n=12), “medium” (n=4),
and “bad” (n=9) variants.
Conclusion
Our results confirm the likelihood that established PD genes are pathogenic and highlight the
importance of ancestrally diverse research in PD. We also show the usefulness of the NBA as a
reliable tool for genotyping of rare variants for PD.
