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

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.

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Journal
npj Parkinson s Disease
Published
2026-05-22
DOI
https://doi.org/10.1038/s41531-026-01349-0
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Germaine Hiu-Fai Chan, Siti Hajar Md Desa, Mong‐Hsun Tsai, Prashanth Lingappa Kukkle et al.
npj Parkinson s Disease
Genetic Associations and Epidemiology
article

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

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

Abstract

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.

npj Parkinson s Disease
Jikei University School of Medicine (JP), Ulsan College (KR), Kyrgyz State Medical Academy (KG), Ministry of Health and Welfare (KR), Alion Science and Technology (United States) (US), Seoul National University (KR), Central South University (CN), Nizam's Institute of Medical Sciences (IN), National Taiwan University of Science and Technology (TW), National University of Singapore (SG), National Taiwan University (TW), Nanyang Technological University (SG), Chang Gung University (TW), Murdoch University (AU), Capital Medical University (CN), Hanoi Medical University (VN), Yonsei University (KR), Hong Kong University of Science and Technology (HK), National Central University (TW), Singapore General Hospital (SG), Sichuan University (CN), Severance Hospital (KR), Sree Chitra Thirunal Institute for Medical Sciences and Technology (IN), RIKEN Center for Brain Science (JP), Seoul Metropolitan Government (KR), University Kebangsaan Malaysia Medical Centre (MY), Asan Medical Center (KR), Seoul National University Hospital (KR), University of Malaya (MY), Juntendo University (JP), University of Ulsan (KR), International Islamic University Malaysia (MY), Data Tecnica International (United States) (US), West China Hospital of Sichuan University (CN), Chonnam National University Hospital (KR), Landseed Hospital (TW), SNUH SMG-SNU Boramae Medical Center (KR), Linkou Chang Gung Memorial Hospital (TW), South Kazakhstan Medical Academy (KZ), Ministry of Health and Welfare (TW), National Institute of Health (AM), National Neuroscience Institute (SG), National Taiwan University Hospital (TW), Juntendo University Urayasu Hospital (JP), Vietnam National Children's Hospital (VN), Perron Institute for Neurological and Translational Science (AU), Shenzhen Institutes of Advanced Technology (CN), Aster Medcity (IN), National Hospital for Neurology and Neurosurgery (GB), Viet Duc Hospital (VN), Taipei Medical University-Shuang Ho Hospital (TW), Xiangya Hospital Central South University (CN), Manipal Hospital (IN), Parkinson's Foundation (US), Queen Elizabeth Hospital (CN), University College London (GB), Menoufia University (EG), All India Institute of Medical Sciences (IN), National Institute of Mental Health and Neurosciences (IN), The University of Tokyo (JP), Zhejiang University (CN), Academia Sinica (TW), National University of Malaysia (MY), University of Hong Kong (HK), National Taipei University (TW)
Michael J. Fox Foundation for Parkinson's Research, Taiwan Biobank
Openalex Percentile: Top 6%
Genetic Associations and Epidemiology
DOIOpen Access PDFOpenAlex
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