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

Taye H. Hamza, Cyrus P. Zabetian, Albert Tenesa, Alain Laederach, Jennifer Montimurro, Dora Yearout, Denise M. Kay, Kimberly F. Doheny, Justin Paschall, Elizabeth Pugh, Victoria I. Kusel, Randall Collura, John Roberts, Alida Griffith, Ali Samii, William K Scott, John Nutt, Stewart A. Factor, Haydeh Payami

Research output: Contribution to journalArticle

416 Citations (Scopus)

Abstract

Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.

Original languageEnglish
Pages (from-to)781-785
Number of pages5
JournalNature Genetics
Volume42
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

Parkinson Disease
HLA-DR alpha-Chains
Research
HLA-DQ Antigens
Genome-Wide Association Study
Microglia
HLA-DR Antigens
Pharmaceutical Preparations
Meta-Analysis
Immune System
Anti-Inflammatory Agents
Up-Regulation
Antigens
Brain

ASJC Scopus subject areas

  • Genetics

Cite this

Hamza, T. H., Zabetian, C. P., Tenesa, A., Laederach, A., Montimurro, J., Yearout, D., ... Payami, H. (2010). Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nature Genetics, 42(9), 781-785. https://doi.org/10.1038/ng.642

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.

In: Nature Genetics, Vol. 42, No. 9, 01.09.2010, p. 781-785.

Research output: Contribution to journalArticle

Hamza, TH, Zabetian, CP, Tenesa, A, Laederach, A, Montimurro, J, Yearout, D, Kay, DM, Doheny, KF, Paschall, J, Pugh, E, Kusel, VI, Collura, R, Roberts, J, Griffith, A, Samii, A, Scott, WK, Nutt, J, Factor, SA & Payami, H 2010, 'Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.', Nature Genetics, vol. 42, no. 9, pp. 781-785. https://doi.org/10.1038/ng.642
Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nature Genetics. 2010 Sep 1;42(9):781-785. https://doi.org/10.1038/ng.642
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. In: Nature Genetics. 2010 ; Vol. 42, No. 9. pp. 781-785.
@article{7d66fea2522449fc934feedf1cf4105d,
title = "Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.",
abstract = "Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.",
author = "Hamza, {Taye H.} and Zabetian, {Cyrus P.} and Albert Tenesa and Alain Laederach and Jennifer Montimurro and Dora Yearout and Kay, {Denise M.} and Doheny, {Kimberly F.} and Justin Paschall and Elizabeth Pugh and Kusel, {Victoria I.} and Randall Collura and John Roberts and Alida Griffith and Ali Samii and Scott, {William K} and John Nutt and Factor, {Stewart A.} and Haydeh Payami",
year = "2010",
month = "9",
day = "1",
doi = "10.1038/ng.642",
language = "English",
volume = "42",
pages = "781--785",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.

AU - Hamza, Taye H.

AU - Zabetian, Cyrus P.

AU - Tenesa, Albert

AU - Laederach, Alain

AU - Montimurro, Jennifer

AU - Yearout, Dora

AU - Kay, Denise M.

AU - Doheny, Kimberly F.

AU - Paschall, Justin

AU - Pugh, Elizabeth

AU - Kusel, Victoria I.

AU - Collura, Randall

AU - Roberts, John

AU - Griffith, Alida

AU - Samii, Ali

AU - Scott, William K

AU - Nutt, John

AU - Factor, Stewart A.

AU - Payami, Haydeh

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.

AB - Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.

UR - http://www.scopus.com/inward/record.url?scp=77956646167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956646167&partnerID=8YFLogxK

U2 - 10.1038/ng.642

DO - 10.1038/ng.642

M3 - Article

VL - 42

SP - 781

EP - 785

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -