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

Yung‐Tsai Chu, Yu-An Su, Chin‐Hsien Lin, Chun‐Hwei Tai, Yih-Ru Wu, Chien-Tai Hong, Yu-Wei Chen, Mong‐Hsun Tsai, John Hardy, Kin Ying Mok

Ещё 87 авторов

Ruey‐Meei Wu, Ji-Feng Guo, Bei-sha Tang, Huifeng Shang, Chunyu Li, Huong Thi Thanh Nguyen, Thi Thanh Huyen Vu, Anh Tuan Nguyen, Nancy Y. Ip, Amy K.Y. Fu, Fanny C.F. Ip, Xiaopu Zhou, Han Cao, Germaine Hiu Fai Chan, Nelson Yuk-Fai Cheung, Wing-Chi Fong, Phillip Chan, Norlinah Mohamed Ibrahim, Shahrul Azmin, Nor Azian Abdul Murad, Siti Aishah Sulaiman, Siti Hajar Md Desa, Wael Mohamed, Sulev Kõks, Abigail L. Pfaff, Lewis M. Singleton, Yun Joong Kim, Seok Jong Chung, Seong-Min Choi, Yu Chen, Yuewen Chen, Tao Ye, Hsiu-Chuan Wu, Tomotaka Shiraishi, Hidetomo Murakami, Renpei Sengoku, Nobutaka Hattori, Manabu Funayama, Tatsushi Toda, Wataru Satake, Kotaro Ogaki, Kenya Nishioka, Andrew Singleton, Mike A. Nalls, Cornelis Blauwendraat, Global Parkinson’s Genetics Program, Pin‐Jui Kung, Serena Wu, Kai Shi Lim, Yi Wen Tay, Azlina Ahmad‐Annuar, Tzi Shin Toh, Shen‐Yang Lim, Ai Huey Tan, Jia Lun Lim, Lei Cheng Lit, Anis Nadhirah Khairul Anuar, Hans Xing Ding, Elaine Guo Yan Chew, Jia Nee Foo, Eng‐King Tan, Hiroyo Yoshino, Rauan B. Kaiyrzhanov, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Mariam Isayan, Samson G. Khachatryan, Zaruhi D. Tavadyan, Han-Joon Kim, Jee‐Young Lee, Sun Ju Chung, Beomseok Jeon, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Germaine Hiu-Fai Chan, Phillip Chan, Asha Kishore, Kalikavil Puthanveedu Divya, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Henry Houlden

2026

Полный текст Открытый доступ: Gold Метаданные (CSL-JSON)
DOI 10.1038/s41531-026-01349-0
Достоверность данных 85 высокая
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Аннотация

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.