Parkinson Disease Pathogenic Variants: Cross-Ancestry Analysis and Microarray Data Validation

帕金森病致病变异:跨种族分析和微阵列数据验证

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Abstract

BACKGROUND AND OBJECTIVES: Known pathogenic variants (PVs) in Parkinson disease (PD) contribute to disease development but have yet to be fully explored by arrays on a large scale. This study evaluated genotyping success of the NeuroBooster array (NBA) and determined the frequencies of PVs across ancestries. METHODS: We analyzed the presence and allele frequency of PVs 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 (GP2) data set. Cluster plots were used to assess the quality of PVs genotyped on NBA. RESULTS: Genes previously predicted to have high or very high confidence of causing PD tend to have more PVs and are present across ancestry groups. Of 34 known PD gene PVs assessed, 25 were typed by NBA and classified as "good" (n = 12), "medium" (n = 4), or "bad" (n = 9) quality variants. DISCUSSION: 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 the genotyping of rare variants of PD.

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