An African ancestry-enriched H1 sub-haplotype challenges MAPT haplotype assignment and reveals distinct tau regulatory programs.

An African ancestry-enriched H1 sub-haplotype at 17q21.31 reveals distinct tau regulation and challenges existing MAPT haplotype classification.

• Why it matters: Understanding genetic variation across ancestries is crucial for accurate disease risk assessment and targeted therapies in neurodegenerative disorders involving tau pathology.
• What they did: Using long-read sequencing, transcriptomics, and functional assays, the study identified H1_A, a novel non-inverted sub-haplotype enriched in individuals of African ancestry, carrying rs8070723.
• The result: This discovery highlights ancestry-specific regulatory programs affecting tau expression and cellular functions, improving interpretation of MAPT-related disease risk across diverse populations.