Linkage disequilibrium and association of MAPT H1 in Parkinson disease.

Skipper, Lisa; Wilkes, Kristen; Toft, Mathias; Baker, Matthew; Lincoln, Sarah; Hulihan, Mary; Ross, Owen A; Hutton, Mike et al. · Am J Hum Genet · 2004

case_control · Level III

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Abstract

The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes--in age/sex-matched PD cases and controls from central Norway--we have refined the disease association to within an approximately 90-kb interval of the 5' end of the MAPT locus.

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