Analysis of rare Parkinson’s disease variants in millions of people

Analysis of rare Parkinson’s disease variants in millions of people

2024 | Vanessa Pitz, Mary B. Makarious, Sara Bandres-Ciga, Hirotaka Iwaki, 23andMe Research Team, Andrew B. Singleton, Mike Nalls, Karl Heilbron, Cornelis Blauwewendraat
This study conducted a large-scale replication of rare variants associated with Parkinson's disease (PD) using data from three major cohorts: 23andMe, UK Biobank, and AMP-PD. The analysis included 27,590 PD cases, 6,701 PD proxies, and 3,106,080 controls. Based on well-known PD genes, 834 variants were selected for analysis. A meta-analysis of the data from all three studies resulted in five significant variants after Bonferroni correction, including variants in *GBA1* and *LRRK2*. Additionally, eight other variants were identified as strong candidates for their association with PD. The study provides the largest rare variant meta-analysis to date, offering insights into confirmed and newly identified variants associated with PD. It also highlights the complexities of studying rare variants in large-scale cohorts.This study conducted a large-scale replication of rare variants associated with Parkinson's disease (PD) using data from three major cohorts: 23andMe, UK Biobank, and AMP-PD. The analysis included 27,590 PD cases, 6,701 PD proxies, and 3,106,080 controls. Based on well-known PD genes, 834 variants were selected for analysis. A meta-analysis of the data from all three studies resulted in five significant variants after Bonferroni correction, including variants in *GBA1* and *LRRK2*. Additionally, eight other variants were identified as strong candidates for their association with PD. The study provides the largest rare variant meta-analysis to date, offering insights into confirmed and newly identified variants associated with PD. It also highlights the complexities of studying rare variants in large-scale cohorts.
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[slides and audio] Analysis of rare Parkinson%E2%80%99s disease variants in millions of people