An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy

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 dif...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945475/
https://www.ncbi.nlm.nih.gov/pubmed/24603599
http://dx.doi.org/10.1371/journal.pgen.1004211
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author 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
author_facet 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
author_sort Li, Yun
collection PubMed
description 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.
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spelling pubmed-39454752014-03-12 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 PLoS Genet Research Article 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. Public Library of Science 2014-03-06 /pmc/articles/PMC3945475/ /pubmed/24603599 http://dx.doi.org/10.1371/journal.pgen.1004211 Text en © 2014 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title_full An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title_fullStr An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title_full_unstemmed An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title_short An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy
title_sort epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945475/
https://www.ncbi.nlm.nih.gov/pubmed/24603599
http://dx.doi.org/10.1371/journal.pgen.1004211
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