Genome-Wide Association and Population-Tailored Polygenic Risk for Parkinson’s Disease in Taiwan

Abstract Parkinson’s disease genetics remain under-characterized in East Asians. We recruited a Taiwanese case–control cohort (2,245 PD; 2,147 controls), genotyped on the Illumina NeuroBooster Array, and imputed 7.6 million variants using the Taiwan Biobank reference. Logistic-regression GWAS identified genome-wide significant signals at SNCA and MCCC1 ; we also observed suggestive associations at GCH1, PPARGC1A and GALNT13 . Haplotype analyses delineated an East Asian SNCA risk haplotype and confirmed effects at LRRK2 p.G2385R and p.Rorg8P. Moreover, we have discovered, for the first time, a gene dosage effect of LRRK2 Asian variants. A European-derived PRS (Nalls 2019) showed modest discrimination in our cohort (AUC 0.590); incorporating Asian and Taiwan-specific variants increased the AUC to 0.615 (DeLong p