Genome-wide association and population-tailored polygenic risk for Parkinson’s disease in Taiwan

Chu Y.-T.; Su Y.-A.; Lin C.-H.; Tai C.-H.; Wu Y.-R.; Hong C.-T.; Chen Y.-W.; Tsai M.-H.; Hardy J.; Mok K.-Y.; Wu R.-M.; Blauwendraat C.; Nalls M.A.; Singleton A.B.; Nishioka K.; Ogaki K.; Satake W.; Toda T.; Funayama M.; Hattori N.; Sengoku R.; Murakami H.; Shiraishi T.; Wu H.-C.; Ye T.; Chen Y.; Chen Y.; Choi S.-M.; Chung S.J.; Kim Y.J.; Singleton L.; Pfaff A.; Koks S.; Mohamed W.; Md Desa S.H.; Sulaiman S.A.; Murad N.A.A.; Azmin S.; Ibrahim N.M.; Chan P.; Fong W.-C.; Cheung N.Y.-F.; Chan G.H.F.; Mok K.Y.; Cao H.; Zhou X.; Ip F.C.F.; Fu A.K.Y.; Ip N.Y.; Nguyen A.T.; Vu T.T.H.; Nguyen H.T.T.; Li C.; Shang H.; Tang B.-S.; Guo J.-F.; Atadzhanov M.; Foroud T.; Xie T.; Walker R.; Alcalay R.; Albin R.; Shulman L.; Dean M.; Ruffrage L.; Chahine L.M.; Marek K.; Markopoulou K.; Kieburtz K.; Nuytemans K.; Shulman J.; Inca-Martinez M.; Jankovic J.; Lubbe S.; Mencacci N.E.; Keller Sarmiento I.J.; Chen H.; Beach T.; Serrano G.E.; Dumanis S.; Riley E.; Williamson J.; Shamim E.; Hall D.; Wegel C.; Pantazis C.B.; Cruchaga C.; Jonas C.; Sobering A.K.; Sherer T.; Chowdhury S.; Louie N.; Kuhl M.; Murphy K.; Solle J.C.; Comart C.; Fiske B.; Casey B.; Siddiqi B.; O’Grady A.; Marsili L.; Espay A.; Stott S.; Love S.; Lewis P.A.; Williams N.; Mok K.Y.; Grosset D.; Bale C.; Carroll C.; Obese V.; Jasaitye S.; Weil R.; Okunoye O.; Wood N.; Morris H.; Stafford E.J.; Schapira A.; Schrag A.; Martínez-Carrasco A.; Genc G.; Ertan S.; Çakmak Ö.Ö.; Başak A.N.; Sassi S.B.; Amouri R.; Krack P.; Zweier C.; El-Sadig S.; Pastor P.; Beyer K.; Hoenicka J.; Alvarez I.; Cubo E.; Bardien S.; Carr J.; Amod F.; Umair M.; Al Mubarak B.; Iakovenko E.; Vinuela A.; Cornejo-Olivas M.; Ur-Rehman S.; Tan M.; Pihlstrøm L.; Aasly J.O.; Ojo O.; Pitcher T.L.; Anderson T.J.; Reayes-Perez P.; Rodriguez-Violante M.; Martinez-Ramirez D.; Krüger R.; Schirinzi T.; Parnetti L.; Avenali M.; Valente E.M.; Quattrone A.; Medina A.; Stamelou M.; Stefanis L.; Tarnanas I.; Dagklis I.; Hadjigeorgiou G.; Xiromerisiou G.; Dardiotis E.; Akpalu A.; Groppa S.; Fang Z.-H.; Gasser T.; Sharma M.; Höglinger G.; Hopfner F.; Mollenhauer B.; Illarionova A.; Lange L.M.; Lohmann K.; Junker J.; Trinh J.; Madoev H.; Vollstedt E.-J.; Klein C.; Westenberger A.; Corvol J.-C.; Brice A.; Zewde Y.Z.; Kamel W.A.; Salama M.; Hernandez A.; del Rio M.J.; Orozco J.; Arboleda G.; Bustamante M.L.; Miranda M.; Olguin P.; Galleguillos B.P.; Monchi O.; Fon T.; Fon E.A.; Camargos S.; Tumas V.; Rieder C.; Zimprich A.; Rentería M.E.; Ellis M.; Kumar K.; Hunter J.; Shepherd C.E.; Kauffman M.; Gatto E.M.; Okubadejo N.; Rizig M.; Screven L.; Houlden H.; Akçimen F.; Bandres-Ciga S.; Koretsky M.J.; Lee P.S.; Periñan M.T.; Nguyen T.; Nguyen D.; Rosales R.; Doquenia M.L.; Ojha R.; Tserensodnom B.; Salari M.; Borgohain R.; Rajan R.; Kukkle P.L.; Pal P.; Divya K.P.; Kishore A.; Ip N.; Chan G.H.-F.; Luo W.; Chan P.; Guo J.; Shang H.; Tang B.; Jeon B.; Chung S.J.; Lee J.-Y.; Kim H.-J.; Tavadyan Z.; Khachatryan S.; Isayan M.; Shambetova C.; Kaishibayeva G.; Karimova A.; Kaiyrzhanov R.; Yoshino H.; Tan E.-K.; Foo J.N.; Chew E.G.Y.; Ding H.X.; Anuar A.N.K.; Lit L.-C.; Lim J.L.; Tan A.H.; Lim S.-Y.; Toh T.S.; Ahmad-Annuar A.; Tay Y.W.; Lim K.S.; Wu S.; Kung P.-J. · npj Parkinson's Disease (2026) · DOI: 10.1038/s41531-026-01349-0

Resumen

Genetic risk factors for Parkinson’s disease (PD) remain under-characterized in East Asian populations. We assembled a Taiwanese case–control cohort (2245 PD; 2147 controls), genotyped participants using the Illumina NeuroBooster Array, and imputed 7.6 million variants with the Taiwan Biobank reference panel. Logistic-regression GWAS identified genome-wide significant associations at SNCA and MCCC1, with the lead SNCA signal located in intron 4; conditional and joint analyses suggested an additional 5′ SNCA component. We observed suggestive associations at GCH1, PPARGC1A, and GALNT13. Locus-focused haplotype analyses refined the SNCA signal, delineating an East Asian–enriched risk haplotype, and confirmed risk effects of LRRK2 p.G2385R and p.R1628P, including evidence consistent with a gene-dosage effect. A European-derived PRS showed modest discrimination in our cohort (AUC 0.59), while incorporating East Asian and Taiwan-relevant variants improved performance (AUC 0.62). Together, these results define the genetic architecture of PD in Taiwan, highlight shared and population-enriched risk components, and support ancestry-aware PRS construction for improved risk stratification. © The Author(s) 2026.