Abstract
LRRK2 variants are key genetic risk factors for Parkinson's Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: P(FDR) = 1.61 × 10(-22), Non-synonymous: P(FDR) = 1.54 × 10(-23), CADD > 20: P(FDR) = 3.09 × 10(-24)). Excluding the p.G2019S variant nullified this effect. Nominal associations were found in the ANK and Roc-COR domains, with potentially protective variants, p.R793M and p.Q1353K.