Exploring MAPT-containing H1 and H2 haplotypes in Parkinson's disease across diverse populations.
Exploring MAPT-containing H1 and H2 haplotypes in Parkinson's disease across diverse populations.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
US · Author affiliation · country only
DataTecnica, Washington, DC, USALocation evidence
MX · Author affiliation · country only
Laboratorio Internacional de Investigación Sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Queretaro, Mexico.Location evidence
Kuala Lumpur, MY · Author affiliation
Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Location evidence
Lagos, NG · Author affiliation
Department of Anatomy, College of Medicine, University of Lagos, Nigeria.Location evidence
Bethesda, US · Author affiliation
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 20892, USA.Location evidence
London, GB · Author affiliation
Department of Clinical and Movement Neurosciences and Movement Disorders Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.Location evidence
Montréal, CA · Author affiliation
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.Location evidence
Québec, CA · Author affiliation
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.Location evidence
Lund, SE · Author affiliation
Translational Neurogenetics Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.Location evidence
Publication status: preprint
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Original 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.