Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci
Abstract Background Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial...
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doaj-e855fad797a54c078bf1a17639f6a8fc2020-11-24T21:30:54ZengBMCMolecular Neurodegeneration1750-13262018-07-0113111010.1186/s13024-018-0267-3Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility lociMonica Y. Sanchez-Contreras0Naomi Kouri1Casey N. Cook2Daniel J. Serie3Michael G. Heckman4NiCole A. Finch5Richard J. Caselli6Ryan J. Uitti7Zbigniew K. Wszolek8Neill Graff-Radford9Leonard Petrucelli10Li-San Wang11Gerard D. Schellenberg12Dennis W. Dickson13Rosa Rademakers14Owen A. Ross15Department of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Health Sciences Research, Mayo ClinicDepartment of Health Sciences Research, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neuroscience, Mayo ClinicPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of PennsylvaniaPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicAbstract Background Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial inheritance have been identified and the common MAPT H1haplotype is a major genetic risk factor. Due to the relatively low prevalence of PSP, large sample sizes can be difficult to achieve, and this has limited the ability to detect true genetic risk factors at the genome-wide statistical threshold for significance in GWAS data. With this in mind, in this study we genotyped the genetic variants that displayed the strongest degree of association with PSP (P<1E-4) in the previous GWAS in a new cohort of 533 pathologically-confirmed PSP cases and 1172 controls, and performed a combined analysis with the previous GWAS data. Results Our findings validate the known association of loci at MAPT, MOBP, EIF2AK3 and STX6 with risk of PSP, and uncover novel associations with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants, both of which were classified as non-significant in the original GWAS. Conclusions Resolving the genetic architecture of PSP will provide mechanistic insights and nominate candidate genes and pathways for future therapeutic intervention strategies.http://link.springer.com/article/10.1186/s13024-018-0267-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Monica Y. Sanchez-Contreras Naomi Kouri Casey N. Cook Daniel J. Serie Michael G. Heckman NiCole A. Finch Richard J. Caselli Ryan J. Uitti Zbigniew K. Wszolek Neill Graff-Radford Leonard Petrucelli Li-San Wang Gerard D. Schellenberg Dennis W. Dickson Rosa Rademakers Owen A. Ross |
spellingShingle |
Monica Y. Sanchez-Contreras Naomi Kouri Casey N. Cook Daniel J. Serie Michael G. Heckman NiCole A. Finch Richard J. Caselli Ryan J. Uitti Zbigniew K. Wszolek Neill Graff-Radford Leonard Petrucelli Li-San Wang Gerard D. Schellenberg Dennis W. Dickson Rosa Rademakers Owen A. Ross Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci Molecular Neurodegeneration |
author_facet |
Monica Y. Sanchez-Contreras Naomi Kouri Casey N. Cook Daniel J. Serie Michael G. Heckman NiCole A. Finch Richard J. Caselli Ryan J. Uitti Zbigniew K. Wszolek Neill Graff-Radford Leonard Petrucelli Li-San Wang Gerard D. Schellenberg Dennis W. Dickson Rosa Rademakers Owen A. Ross |
author_sort |
Monica Y. Sanchez-Contreras |
title |
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci |
title_short |
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci |
title_full |
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci |
title_fullStr |
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci |
title_full_unstemmed |
Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci |
title_sort |
replication of progressive supranuclear palsy genome-wide association study identifies slco1a2 and dusp10 as new susceptibility loci |
publisher |
BMC |
series |
Molecular Neurodegeneration |
issn |
1750-1326 |
publishDate |
2018-07-01 |
description |
Abstract Background Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial inheritance have been identified and the common MAPT H1haplotype is a major genetic risk factor. Due to the relatively low prevalence of PSP, large sample sizes can be difficult to achieve, and this has limited the ability to detect true genetic risk factors at the genome-wide statistical threshold for significance in GWAS data. With this in mind, in this study we genotyped the genetic variants that displayed the strongest degree of association with PSP (P<1E-4) in the previous GWAS in a new cohort of 533 pathologically-confirmed PSP cases and 1172 controls, and performed a combined analysis with the previous GWAS data. Results Our findings validate the known association of loci at MAPT, MOBP, EIF2AK3 and STX6 with risk of PSP, and uncover novel associations with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants, both of which were classified as non-significant in the original GWAS. Conclusions Resolving the genetic architecture of PSP will provide mechanistic insights and nominate candidate genes and pathways for future therapeutic intervention strategies. |
url |
http://link.springer.com/article/10.1186/s13024-018-0267-3 |
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