Linkage disequilibrium and association of MAPT H1 in Parkinson disease

Lisa Skipper; Kristen Wilkes; Mathias Toft; Matthew Baker; Sarah Lincoln; Mary Hulihan; Owen A. Ross; Mike Hutton; Jan Aasly; Matthew Farrer

doi:10.1086/424492

Linkage disequilibrium and association of MAPT H1 in Parkinson disease

Lisa Skipper, Kristen Wilkes, Mathias Toft, Matthew Baker, Sarah Lincoln, Mary Hulihan, Owen A. Ross, Mike Hutton, Jan Aasly, Matthew Farrer

Neuroscience

Research output: Contribution to journal › Article › peer-review

124 Scopus citations

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 ∼90-kb interval of the 5′ end of the MAPT locus.

Original language	English (US)
Pages (from-to)	669-677
Number of pages	9
Journal	American journal of human genetics
Volume	75
Issue number	4
DOIs	https://doi.org/10.1086/424492
State	Published - Oct 2004

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1086/424492

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title = "Linkage disequilibrium and association of MAPT H1 in Parkinson disease",

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 ∼90-kb interval of the 5′ end of the MAPT locus.",

author = "Lisa Skipper and Kristen Wilkes and Mathias Toft and Matthew Baker and Sarah Lincoln and Mary Hulihan and Ross, {Owen A.} and Mike Hutton and Jan Aasly and Matthew Farrer",

note = "Funding Information: We thank the participants; Dr. Corrinne Aasly, for recruitment of control subjects; and Minnie Schreiber, for technical assistance. M.F. and the study were funded by the Society for Progressive Supranuclear Palsy, the Norwegian Parkinson{\textquoteright}s Association, and Reberg{\textquoteright}s Legacy. O.A.R. was a Visiting Fellow funded by the R&D Office, Health and Personal Social Services, Northern Ireland. ",

year = "2004",

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doi = "10.1086/424492",

language = "English (US)",

volume = "75",

pages = "669--677",

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AU - Skipper, Lisa

AU - Wilkes, Kristen

AU - Toft, Mathias

AU - Baker, Matthew

AU - Lincoln, Sarah

AU - Hulihan, Mary

AU - Ross, Owen A.

AU - Hutton, Mike

AU - Aasly, Jan

AU - Farrer, Matthew

N1 - Funding Information: We thank the participants; Dr. Corrinne Aasly, for recruitment of control subjects; and Minnie Schreiber, for technical assistance. M.F. and the study were funded by the Society for Progressive Supranuclear Palsy, the Norwegian Parkinson’s Association, and Reberg’s Legacy. O.A.R. was a Visiting Fellow funded by the R&D Office, Health and Personal Social Services, Northern Ireland.

PY - 2004/10

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N2 - 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 ∼90-kb interval of the 5′ end of the MAPT locus.

AB - 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 ∼90-kb interval of the 5′ end of the MAPT locus.

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Linkage disequilibrium and association of MAPT H1 in Parkinson disease

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