Exome Sequencing Identifies Population-Specific Genetic Risk Factors for Progressive Supranuclear Palsy in Asia

Chen PS 1 , Lin RJ 2 , Chen HY 1 , Cheng L 3 , Hung MZ 2 , Lee NC 2 Show all authors , Hsu JS 4 , Fan SP 1 , Li CH 1 , Tai CH 1 , Luo W 5 , Zheng X 5 , Chiang HL 6 , Chen CY 6 , Wu YR 7 , Lee TL 8 , Chang YY 9 , Lan MY 9 , Chang HC 10 , Lu CS 10 , Huang SY 11 , Kim HJ 12 , Lee JY 12 , Shin JH 12 , Saranza G 13 , Nomura T 14 , Yaguchi H 14 , Lee WP 15 , Toh TS 16 , Tay YW 17 , Ahmad-Annuar A 17 , Ooi JCE 18 , Chia YK 18 , Anuar ANK 19 , Ng ASL 20 , Tan YJ 20 , Tan AH 16 , Tan EK 20 , Chan CC 3 , Yabe I 14 , Lim SY 16 , Lin CH 1

Affiliations 

  • 1 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
  • 2 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
  • 3 Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan
  • 4 Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
  • 5 Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  • 6 Division of General Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
  • 7 Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • 8 Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • 9 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Center for Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
  • 10 Professor Lu Neurological Clinic, Taoyuan, Taiwan
  • 11 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
  • 12 Departments of Neurology, College of Medicine, Seoul National University, Seoul, Republic of Korea
  • 13 Section of Neurology, Department of Internal Medicine, Chong Hua Hospital, Cebu, Philippines
  • 14 Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • 15 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  • 16 Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 17 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 18 Department of Neurology, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia
  • 19 Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 20 Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore
Mov Disord, 2026 Nov 01.
PMID: 42967813 DOI: 10.1002/mds.70595

Abstract

BACKGROUND: Progressive supranuclear palsy (PSP) is a debilitating primary tauopathy. Although genome-wide association studies have identified risk loci in European populations, the genetic architecture of PSP in Asia remains largely undefined.

OBJECTIVES: We aimed to identify population-specific genetic risk factors in Asian patients with PSP.

METHODS: We performed whole-exome sequencing in 549 patients with PSP recruited across East and Southeast Asia. Variant frequencies were compared with 1492 whole-genome-sequenced controls from the Taiwan Biobank. Novel variants were functionally evaluated using cellular and Drosophila models.

RESULTS: Among 549 patients (mean age at onset 65.1 ± 7.4 years; 60.47% male), 29 (5.28%) carried heterozygous pathogenic or likely pathogenic variants, including 12 novel variants. Additionally, 127 patients (23.13%) harbored 144 rare variants of uncertain significance with minor allele frequency 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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