A meta-analysis of genome-wide association studies identified 17 new Parkinson's disease (PD) risk loci. The study combined data from 6,476 PD cases and 302,042 controls from a 23andMe cohort with a large-scale meta-analysis of over 13,000 PD cases and 95,000 controls, resulting in a total of 26,035 cases and 403,190 controls. This analysis identified 17 novel loci with genome-wide significance (P < 5 × 10⁻⁸). These loci were associated with genes involved in autophagy and lysosomal biology, suggesting potential new drug targets for PD. The study also identified 35 loci with P < 1 × 10⁻⁶, including 15 with genome-wide significance. The results highlight the role of autophagy and lysosomal biology in PD risk. The study used a neurocentric strategy to assign candidate risk genes to the loci, identifying protein-altering or cis-expression quantitative trait locus (cis-eQTL) variants in 29 of the 41 PD loci. The study also found that several of the newly identified PD risk genes are involved in lysosomal biology and autophagy. The identification of these candidate genes allows for the prioritization of functional studies to determine causal genes for PD and possible therapeutic targets. The study also found that the heritability of PD is enriched for histone marks in central nervous system, adrenal, and pancreatic cell types. The study used a neurocentric strategy to nominate candidate genes for PD-associated loci, incorporating seven sources of data to annotate the index variant and linked variants from PD-associated loci. The study also found that several of the PD candidate genes are within the 'druggable' genome, including the previously identified serine/threonine kinase 39 (STK39) and the novel candidate gene inositol 1,4,5-trisphosphate kinase B (ITPKB). The study also identified three transcription factors: SATB1, ZNF184, and TOX3, which may have a role in PD. The study found that the lysosomal pathway was significantly enriched for PD-associated signals, suggesting a key role for lysosomal biology in PD risk. The study also found that several of the PD candidate genes are involved in autophagy, which is a catabolic process that targets long-lived proteins and dysfunctional organelles for lysosomal degradation. The study also found that a strong cis-eQTL for lysine acetyltransferase 8 (KAT8) is associated with PD risk, with lower levels of KAT8 mRNA linked to increased PD risk. The study also found that inhibition of KAT8 was recently shown to decrease autophagic flux.A meta-analysis of genome-wide association studies identified 17 new Parkinson's disease (PD) risk loci. The study combined data from 6,476 PD cases and 302,042 controls from a 23andMe cohort with a large-scale meta-analysis of over 13,000 PD cases and 95,000 controls, resulting in a total of 26,035 cases and 403,190 controls. This analysis identified 17 novel loci with genome-wide significance (P < 5 × 10⁻⁸). These loci were associated with genes involved in autophagy and lysosomal biology, suggesting potential new drug targets for PD. The study also identified 35 loci with P < 1 × 10⁻⁶, including 15 with genome-wide significance. The results highlight the role of autophagy and lysosomal biology in PD risk. The study used a neurocentric strategy to assign candidate risk genes to the loci, identifying protein-altering or cis-expression quantitative trait locus (cis-eQTL) variants in 29 of the 41 PD loci. The study also found that several of the newly identified PD risk genes are involved in lysosomal biology and autophagy. The identification of these candidate genes allows for the prioritization of functional studies to determine causal genes for PD and possible therapeutic targets. The study also found that the heritability of PD is enriched for histone marks in central nervous system, adrenal, and pancreatic cell types. The study used a neurocentric strategy to nominate candidate genes for PD-associated loci, incorporating seven sources of data to annotate the index variant and linked variants from PD-associated loci. The study also found that several of the PD candidate genes are within the 'druggable' genome, including the previously identified serine/threonine kinase 39 (STK39) and the novel candidate gene inositol 1,4,5-trisphosphate kinase B (ITPKB). The study also identified three transcription factors: SATB1, ZNF184, and TOX3, which may have a role in PD. The study found that the lysosomal pathway was significantly enriched for PD-associated signals, suggesting a key role for lysosomal biology in PD risk. The study also found that several of the PD candidate genes are involved in autophagy, which is a catabolic process that targets long-lived proteins and dysfunctional organelles for lysosomal degradation. The study also found that a strong cis-eQTL for lysine acetyltransferase 8 (KAT8) is associated with PD risk, with lower levels of KAT8 mRNA linked to increased PD risk. The study also found that inhibition of KAT8 was recently shown to decrease autophagic flux.