Scholarlink

<p>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 <i>SNCA</i> and <i>MCCC1</i>, with the lead <i>SNCA</i> signal located in intron 4; conditional and joint analyses suggested an additional 5′ <i>SNCA</i> component. We observed suggestive associations at <i>GCH1</i>, <i>PPARGC1A</i>, and <i>GALNT13</i>. Locus-focused haplotype analyses refined the <i>SNCA</i> signal, delineating an East Asian–enriched risk haplotype, and confirmed risk effects of <i>LRRK2</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月22日

查看全文
  • 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,
  • 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,
  • Kin Ying Mok,
  • John Hardy,
  • 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 Koks,
  • Abigail Pfaff,
  • Lewis 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 B. Singleton,
  • Mike A. Nalls,
  • Cornelis Blauwendraat,
  • 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,
  • Manabu Funayama,
  • Hiroyo Yoshino,
  • Rauan Kaiyrzhanov,
  • Altynay Karimova,
  • Gulnaz Kaishibayeva,
  • Cholpon Shambetova,
  • Mariam Isayan,
  • Samson Khachatryan,
  • Zaruhi 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,
  • Nancy Ip,
  • Phillip Chan,
  • Asha Kishore,
  • K. P. Divya,
  • Pramod Pal,
  • Prashanth Lingappa Kukkle,
  • Roopa Rajan,
  • Rupam Borgohain,
  • Mehri Salari,
  • Bayasgalan Tserensodnom,
  • Rajeev Ojha,
  • Maria Leila Doquenia,
  • Raymond Rosales,
  • Duan Nguyen,
  • Toan Nguyen,
  • Maria Teresa Periñan,
  • Paul Suhwan Lee,
  • Mathew J. Koretsky,
  • Sara Bandres-Ciga,
  • Fulya Akçimen,
  • Henry Houlden,
  • Laurel Screven,
  • Mie Rizig,
  • Njideka Okubadejo,
  • Emilia M. Gatto,
  • Marcelo Kauffman,
  • Claire E. Shepherd,
  • Julie Hunter,
  • Kishore Kumar,
  • Melina Ellis,
  • Miguel E. Rentería,
  • Sulev Koks,
  • Alexander Zimprich,
  • Carlos Rieder,
  • Vitor Tumas,
  • Sarah Camargos,
  • Edward A. Fon,
  • Ted Fon,
  • Oury Monchi,
  • Benjamin Pizarro Galleguillos,
  • Patricio Olguin,
  • Marcelo Miranda,
  • Maria Leonor Bustamante,
  • Gonzalo Arboleda,
  • Jorge Orozco,
  • Marlene Jimenez del Rio,
  • Alvaro Hernandez,
  • Mohamed Salama,
  • Walaa A. Kamel,
  • Yared Z. Zewde,
  • Alexis Brice,
  • Jean-Christophe Corvol,
  • Ana Westenberger,
  • Christine Klein,
  • Eva-Juliane Vollstedt,
  • Harutyun Madoev,
  • Joanne Trinh,
  • Johanna Junker,
  • Katja Lohmann,
  • Lara M. Lange,
  • Anastasia Illarionova,
  • Brit Mollenhauer,
  • Franziska Hopfner,
  • Günter Höglinger,
  • Manu Sharma,
  • Thomas Gasser,
  • Zih-Hua Fang,
  • Sergio Groppa,
  • Albert Akpalu,
  • Efthymios Dardiotis,
  • Georgia Xiromerisiou,
  • Georgios Hadjigeorgiou,
  • Ioannis Dagklis,
  • Ioannis Tarnanas,
  • Leonidas Stefanis,
  • Maria Stamelou,
  • Alex Medina,
  • Andrea Quattrone,
  • Enza Maria Valente,
  • Micol Avenali,
  • Lucilla Parnetti,
  • Tommaso Schirinzi,
  • Rejko Krüger,
  • Wael Mohamed,
  • Daniel Martinez-Ramirez,
  • Mayela Rodriguez-Violante,
  • Paula Reayes-Perez,
  • Tim J. Anderson,
  • Toni L. Pitcher,
  • Oluwadamilola Ojo,
  • Jan O. Aasly,
  • Lasse Pihlstrøm,
  • Manuela Tan,
  • Shoaib Ur-Rehman,
  • Mario Cornejo-Olivas,
  • Angel Vinuela,
  • Elena Iakovenko,
  • Bashayer Al Mubarak,
  • Muhammad Umair,
  • Ferzana Amod,
  • Jonathan Carr,
  • Soraya Bardien,
  • Esther Cubo,
  • Ignacio Alvarez,
  • Janet Hoenicka,
  • Katrin Beyer,
  • Pau Pastor,
  • Sarah El-Sadig,
  • Christiane Zweier,
  • Paul Krack,
  • Rim Amouri,
  • Samia Ben Sassi,
  • A. Nazl Başak,
  • Özgür Öztop Çakmak,
  • Sibel Ertan,
  • Gencer Genc,
  • Alejandro Martínez-Carrasco,
  • Anette Schrag,
  • Anthony Schapira,
  • Eleanor J. Stafford,
  • Huw Morris,
  • John Hardy,
  • Nicholas Wood,
  • Olaitan Okunoye,
  • Rimona Weil,
  • Simona Jasaitye,
  • Vida Obese,
  • Camille Carroll,
  • Claire Bale,
  • Donald Grosset,
  • Kin Y. Mok,
  • Nigel Williams,
  • Patrick A. Lewis,
  • Seth Love,
  • Simon Stott,
  • Alberto Espay,
  • Luca Marsili,
  • Alyssa O’Grady,
  • Bernadette Siddiqi,
  • Bradford Casey,
  • Brian Fiske,
  • Charisse Comart,
  • Justin C. Solle,
  • Kaileigh Murphy,
  • Maggie Kuhl,
  • Naomi Louie,
  • Sohini Chowdhury,
  • Todd Sherer,
  • Andrew K. Sobering,
  • Cabell Jonas,
  • Carlos Cruchaga,
  • Caroline B. Pantazis,
  • Claire Wegel,
  • Deborah Hall,
  • Ejaz Shamim,
  • Jared Williamson,
  • Ekemini Riley,
  • Sonya Dumanis,
  • Geidy E. Serrano,
  • Thomas Beach,
  • Honglei Chen,
  • Ignacio Juan Keller Sarmiento,
  • Niccolò E. Mencacci,
  • Steven Lubbe,
  • Joseph Jankovic,
  • Miguel Inca-Martinez,
  • Joshua Shulman,
  • Karen Nuytemans,
  • Karl Kieburtz,
  • Katerina Markopoulou,
  • Kenneth Marek,
  • Lana M. Chahine,
  • Lauren Ruffrage,
  • Marissa Dean,
  • Lisa Shulman,
  • Roger Albin,
  • Roy Alcalay,
  • Ruth Walker,
  • Tao Xie,
  • Tatiana Foroud,
  • Masharip Atadzhanov

摘要

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.