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Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease

Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (P(Pankratz+...

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Autores principales: Hamza, Taye H, Zabetian, Cyrus P, Tenesa, Albert, Laederach, Alain, Montimurro, Jennifer, Yearout, Dora, Kay, Denise M, Doheny, Kimberly F, Paschall, Justin, Pugh, Elizabeth, Kusel, Victoria I, Collura, Randall, Roberts, John, Griffith, Alida, Samii, Ali, Scott, William K, Nutt, John, Factor, Stewart A, Payami, Haydeh
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930111/
https://www.ncbi.nlm.nih.gov/pubmed/20711177
http://dx.doi.org/10.1038/ng.642
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author Hamza, Taye H
Zabetian, Cyrus P
Tenesa, Albert
Laederach, Alain
Montimurro, Jennifer
Yearout, Dora
Kay, Denise M
Doheny, Kimberly F
Paschall, Justin
Pugh, Elizabeth
Kusel, Victoria I
Collura, Randall
Roberts, John
Griffith, Alida
Samii, Ali
Scott, William K
Nutt, John
Factor, Stewart A
Payami, Haydeh
author_facet Hamza, Taye H
Zabetian, Cyrus P
Tenesa, Albert
Laederach, Alain
Montimurro, Jennifer
Yearout, Dora
Kay, Denise M
Doheny, Kimberly F
Paschall, Justin
Pugh, Elizabeth
Kusel, Victoria I
Collura, Randall
Roberts, John
Griffith, Alida
Samii, Ali
Scott, William K
Nutt, John
Factor, Stewart A
Payami, Haydeh
author_sort Hamza, Taye H
collection PubMed
description Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (P(Pankratz+NGRC)=3.2×10(−9)); and detected a novel association with HLA (P(NGRC)=2.9×10(−8)) which replicated in two datasets (P(Meta-analysis)=1.9×10(−10)). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10(−10)) and late-onset (P=2.4×10(−8)) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics.
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spelling pubmed-29301112011-03-01 Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease Hamza, Taye H Zabetian, Cyrus P Tenesa, Albert Laederach, Alain Montimurro, Jennifer Yearout, Dora Kay, Denise M Doheny, Kimberly F Paschall, Justin Pugh, Elizabeth Kusel, Victoria I Collura, Randall Roberts, John Griffith, Alida Samii, Ali Scott, William K Nutt, John Factor, Stewart A Payami, Haydeh Nat Genet Article Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (P(Pankratz+NGRC)=3.2×10(−9)); and detected a novel association with HLA (P(NGRC)=2.9×10(−8)) which replicated in two datasets (P(Meta-analysis)=1.9×10(−10)). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10(−10)) and late-onset (P=2.4×10(−8)) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics. 2010-08-15 2010-09 /pmc/articles/PMC2930111/ /pubmed/20711177 http://dx.doi.org/10.1038/ng.642 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Hamza, Taye H
Zabetian, Cyrus P
Tenesa, Albert
Laederach, Alain
Montimurro, Jennifer
Yearout, Dora
Kay, Denise M
Doheny, Kimberly F
Paschall, Justin
Pugh, Elizabeth
Kusel, Victoria I
Collura, Randall
Roberts, John
Griffith, Alida
Samii, Ali
Scott, William K
Nutt, John
Factor, Stewart A
Payami, Haydeh
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title_full Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title_fullStr Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title_full_unstemmed Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title_short Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease
title_sort common genetic variation in the hla region is associated with late-onset sporadic parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930111/
https://www.ncbi.nlm.nih.gov/pubmed/20711177
http://dx.doi.org/10.1038/ng.642
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