Fig. 1. Rare nonsynonymous gene-based and single-variant analyses in 2,184 PD cases and 69,775 controls identify RAB32, LRRK2 and GBA.

a, The y axis shows the gene-based associations from the ACAT omnibus test including Firth’s logistic regression, SKAT and ACAT-V (two-tailed −log₁₀(P value)) plotted against genomic coordinates on the x axis (GRCh38). The dashed line indicates the exome-wide significance threshold (P = 2.7 × 10⁻⁶). b, Estimated odds ratios (OR) (log transformed, x axis) and 95% confidence intervals (CI) of the exome-wide significant single variants obtained from Firth’s logistic regression. c, Conditional analyses (MAF <0.05) of significant genes using the ACAT omnibus test including Firth’s logistic regression, SKAT and ACAT-V (two-tailed). In red are the unconditioned gene associations and in blue are the conditioned gene associations, adjusted for the significant single variants within the respective gene (p.E365K in GBA, p.G2019S and p.R1441C in LRRK2, and p.S71R in RAB32). d, Single-variant associations in RAB32 estimated using Firth’s logistic regression (y axis; two-tailed −log₁₀(P value)), plotted against coding sequence positions (CDS; x axis).