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An epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy

Li, Yun ; Chen, Jason A ; Sears, Renee L ; Gao, Fuying ; Klein, Eric D ; Karydas, Anna ; Geschwind, Michael D ; Rosen, Howard J ; Boxer, Adam L ; Guo, Weilong ; Pellegrini, Matteo ; Horvath, Steve ; Miller, Bruce L ; Geschwind, Daniel H ; Coppola, Giovanni Copenhaver, Gregory P.

PLoS genetics, 2014-03, Vol.10 (3), p.e1004211-e1004211 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
An epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy
Autor: Li, Yun ; Chen, Jason A ; Sears, Renee L ; Gao, Fuying ; Klein, Eric D ; Karydas, Anna ; Geschwind, Michael D ; Rosen, Howard J ; Boxer, Adam L ; Guo, Weilong ; Pellegrini, Matteo ; Horvath, Steve ; Miller, Bruce L ; Geschwind, Daniel H ; Coppola, Giovanni
Copenhaver, Gregory P.
Assuntos: Biology ; Brain - metabolism ; Brain - pathology ; Chromosomes, Human, Pair 17 ; Degeneration ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Frontotemporal Dementia - genetics ; Frontotemporal Dementia - pathology ; Genetic aspects ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic research ; Genomics ; Haplotypes ; Humans ; Medicine ; Nervous system ; Neurodegenerative Diseases ; Neurological research ; Risk Factors ; Studies ; Supranuclear Palsy, Progressive - genetics ; Supranuclear Palsy, Progressive - pathology ; tau Proteins - genetics ; Tauopathies - etiology ; Tauopathies - genetics ; Tauopathies - pathology
É parte de: PLoS genetics, 2014-03, Vol.10 (3), p.e1004211-e1004211
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: YL DHG GC. Performed the experiments: YL RLS EDK AK WG. Analyzed the data: YL JAC RLS FG WG MP GC. Contributed reagents/materials/analysis tools: AK MDG HJR ALB WG MP SH BLM. Wrote the paper: YL JAC DHG GC.
The authors have declared that no competing interests exist.
Descrição: Little is known about how changes in DNA methylation mediate risk for human diseases including dementia. Analysis of genome-wide methylation patterns in patients with two forms of tau-related dementia--progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)--revealed significant differentially methylated probes (DMPs) in patients versus unaffected controls. Remarkably, DMPs in PSP were clustered within the 17q21.31 region, previously known to harbor the major genetic risk factor for PSP. We identified and replicated a dose-dependent effect of the risk-associated H1 haplotype on methylation levels within the region in blood and brain. These data reveal that the H1 haplotype increases risk for tauopathy via differential methylation at that locus, indicating a mediating role for methylation in dementia pathophysiology.
Editor: United States: Public Library of Science
Idioma: Inglês

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An epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy

Li, Yun ; Chen, Jason A ; Sears, Renee L ; Gao, Fuying ; Klein, Eric D ; Karydas, Anna ; Geschwind, Michael D ; Rosen, Howard J ; Boxer, Adam L ; Guo, Weilong ; Pellegrini, Matteo ; Horvath, Steve ; Miller, Bruce L ; Geschwind, Daniel H ; Coppola, Giovanni Copenhaver, Gregory P.

United States: Public Library of Science

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