A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease

Rejko Krüger, Manu Sharma, Olaf Riess, Thomas Gasser, Christine Van Broeckhoven, Jessie Theuns, Jan Aasly, Grazia Annesi, Anna Rita Bentivoglio, Alexis Brice, Ana Djarmati, Alexis Elbaz, Matthew Farrer, Carlo Ferrarese, J. Mark Gibson, Georgios M. Hadjigeorgiou, Nobutaka Hattori, John P A Ioannidis, Barbara Jasinska-Myga, Christine KleinJean Charles Lambert, Suzanne Lesage, Juei Jueng Lin, Timothy Lynch, George D. Mellick, Francesa de Nigris, Grzegorz Opala, Alessandro Prigione, Aldo Quattrone, Owen A Ross, Wataru Satake, Peter A. Silburn, Eng King Tan, Tatsushi Toda, Hiroyuki Tomiyama, Karin Wirdefeldt, Zbigniew K Wszolek, Georgia Xiromerisiou, Demetrius M. Maraganore

Research output: Contribution to journalArticle

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Abstract

High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium.GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3. kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants.The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I2 estimates 0-28%). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p=0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest.This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume32
Issue number3
DOIs
StatePublished - Mar 2011

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Genetic Association Studies
Parkinson Disease
Molecular Epidemiology
Single Nucleotide Polymorphism
Genes
Parkinson Disease 13
Disease Susceptibility
Age of Onset
Odds Ratio
Population

Keywords

  • Genetics
  • HtrA2
  • Omi
  • PARK13
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease. / Krüger, Rejko; Sharma, Manu; Riess, Olaf; Gasser, Thomas; Van Broeckhoven, Christine; Theuns, Jessie; Aasly, Jan; Annesi, Grazia; Bentivoglio, Anna Rita; Brice, Alexis; Djarmati, Ana; Elbaz, Alexis; Farrer, Matthew; Ferrarese, Carlo; Gibson, J. Mark; Hadjigeorgiou, Georgios M.; Hattori, Nobutaka; Ioannidis, John P A; Jasinska-Myga, Barbara; Klein, Christine; Lambert, Jean Charles; Lesage, Suzanne; Lin, Juei Jueng; Lynch, Timothy; Mellick, George D.; de Nigris, Francesa; Opala, Grzegorz; Prigione, Alessandro; Quattrone, Aldo; Ross, Owen A; Satake, Wataru; Silburn, Peter A.; Tan, Eng King; Toda, Tatsushi; Tomiyama, Hiroyuki; Wirdefeldt, Karin; Wszolek, Zbigniew K; Xiromerisiou, Georgia; Maraganore, Demetrius M.

In: Neurobiology of Aging, Vol. 32, No. 3, 03.2011.

Research output: Contribution to journalArticle

Krüger, R, Sharma, M, Riess, O, Gasser, T, Van Broeckhoven, C, Theuns, J, Aasly, J, Annesi, G, Bentivoglio, AR, Brice, A, Djarmati, A, Elbaz, A, Farrer, M, Ferrarese, C, Gibson, JM, Hadjigeorgiou, GM, Hattori, N, Ioannidis, JPA, Jasinska-Myga, B, Klein, C, Lambert, JC, Lesage, S, Lin, JJ, Lynch, T, Mellick, GD, de Nigris, F, Opala, G, Prigione, A, Quattrone, A, Ross, OA, Satake, W, Silburn, PA, Tan, EK, Toda, T, Tomiyama, H, Wirdefeldt, K, Wszolek, ZK, Xiromerisiou, G & Maraganore, DM 2011, 'A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease', Neurobiology of Aging, vol. 32, no. 3. https://doi.org/10.1016/j.neurobiolaging.2009.11.021
Krüger, Rejko ; Sharma, Manu ; Riess, Olaf ; Gasser, Thomas ; Van Broeckhoven, Christine ; Theuns, Jessie ; Aasly, Jan ; Annesi, Grazia ; Bentivoglio, Anna Rita ; Brice, Alexis ; Djarmati, Ana ; Elbaz, Alexis ; Farrer, Matthew ; Ferrarese, Carlo ; Gibson, J. Mark ; Hadjigeorgiou, Georgios M. ; Hattori, Nobutaka ; Ioannidis, John P A ; Jasinska-Myga, Barbara ; Klein, Christine ; Lambert, Jean Charles ; Lesage, Suzanne ; Lin, Juei Jueng ; Lynch, Timothy ; Mellick, George D. ; de Nigris, Francesa ; Opala, Grzegorz ; Prigione, Alessandro ; Quattrone, Aldo ; Ross, Owen A ; Satake, Wataru ; Silburn, Peter A. ; Tan, Eng King ; Toda, Tatsushi ; Tomiyama, Hiroyuki ; Wirdefeldt, Karin ; Wszolek, Zbigniew K ; Xiromerisiou, Georgia ; Maraganore, Demetrius M. / A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 3.
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abstract = "High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium.GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3. kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants.The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I2 estimates 0-28{\%}). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p=0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest.This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide.",
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AU - Krüger, Rejko

AU - Sharma, Manu

AU - Riess, Olaf

AU - Gasser, Thomas

AU - Van Broeckhoven, Christine

AU - Theuns, Jessie

AU - Aasly, Jan

AU - Annesi, Grazia

AU - Bentivoglio, Anna Rita

AU - Brice, Alexis

AU - Djarmati, Ana

AU - Elbaz, Alexis

AU - Farrer, Matthew

AU - Ferrarese, Carlo

AU - Gibson, J. Mark

AU - Hadjigeorgiou, Georgios M.

AU - Hattori, Nobutaka

AU - Ioannidis, John P A

AU - Jasinska-Myga, Barbara

AU - Klein, Christine

AU - Lambert, Jean Charles

AU - Lesage, Suzanne

AU - Lin, Juei Jueng

AU - Lynch, Timothy

AU - Mellick, George D.

AU - de Nigris, Francesa

AU - Opala, Grzegorz

AU - Prigione, Alessandro

AU - Quattrone, Aldo

AU - Ross, Owen A

AU - Satake, Wataru

AU - Silburn, Peter A.

AU - Tan, Eng King

AU - Toda, Tatsushi

AU - Tomiyama, Hiroyuki

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew K

AU - Xiromerisiou, Georgia

AU - Maraganore, Demetrius M.

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KW - Omi

KW - PARK13

KW - Parkinson's disease

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