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<p>Variation at the 17q21.31 locus, which contains the gene encoding microtubule-associated protein tau (<i>MAPT</i>), 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.</p>

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

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  • 发表日期：

    2026年6月24日

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摘要

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.