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Publications

Journal Article Ahead of print

PubMed: 42342696 DOI: 10.1038/s41531-026-01394-9

Exploring MAPT-containing H1 and H2 haplotypes in Parkinson's disease across diverse populations.

NPJ Parkinsons Dis

Authors: Paula Reyes-Pérez, Jia Wei Hor, Tzi Shin Toh, Arinola O Sanyaolu, Caroline B Pantazis, Thiago Peixoto Leal, Sheila Yeboah, Sara Bandres-Ciga, Huw R Morris, Mary B Makarious, Konstantin Senkevich, Hampton Leonard, Kajsa Atterling Brolin

Affiliations

  • Laboratorio Internacional de Investigación Sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Mexico.
  • Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala lumpur, Malaysia.
  • Department of Anatomy, College of Medicine, University of Lagos, Lagos, Nigeria.
  • Coalition for Aligning Science, Washington, WA, USA.
  • Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Department of Clinical and Movement Neurosciences and Movement Disorders Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • DataTecnica, Washington, DC, USA.
  • The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, QC, Canada.
  • Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada.
  • Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada.
  • Translational Neurogenetics Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Preventive Neurology Unit, Centre for Prevention, Detection and Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, EC1M 6BQ, London, UK.

Abstract

Variation at the 17q21.31 locus, which contains the gene encoding microtubule-associated protein tau (MAPT), has been associated with neurodegenerative disorders, including Parkinson's disease (PD). This highly complex locus is characterized by two broadly defined haplotypes: H1 and the inverted H2 haplotype. While H1 has been associated with an increased PD risk and is present in all ancestry populations, H2 is enriched in individuals of European ancestry. So far, few studies have explored the H1 association with PD in non-European ancestries. Here, we investigated the haplotype and subhaplotype frequencies of H1 and H2 in 20,507 PD patients and 11,841 controls across eleven different ancestry groups from the Global Parkinson's Genetics Program (GP2) and the Latin American Research consortium on the GEnetics of Parkinson's Disease (LARGE-PD). Our results strongly support the involvement of the H1 haplotype in PD risk in individuals of European ancestry, with additional evidence suggesting an association across diverse ancestry groups. Additionally, we observed significant variation in the H1 subhaplotype frequencies within populations, highlighting the complexity of this genomic region and the relevance of its study in diverse ancestries to gain a more comprehensive understanding of the role this locus plays in neurodegenerative disease risk.

MeSH

Genes, Parkinson Disease, Haplotypes, Neurodegenerative Diseases