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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 and Brice, Alexis, et al. (2011) In Neurobiology of Aging 32(3). p.9-548
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... (More)

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; I(2) 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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Aged, Chi-Square Distribution, Cohort Studies, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Meta-Analysis as Topic, Middle Aged, Mitochondrial Proteins, Parkinson Disease, Polymorphism, Single Nucleotide, Serine Endopeptidases, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
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Neurobiology of Aging
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32
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3
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9 - 548
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Elsevier
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  • scopus:79952900158
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1558-1497
DOI
10.1016/j.neurobiolaging.2009.11.021
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English
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aa038b7b-07d0-42cc-830a-d266785bec48
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@article{aa038b7b-07d0-42cc-830a-d266785bec48,
  abstract     = {<p>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; I(2) 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.</p>},
  author       = {Krüger, Rejko and Sharma, Manu and Riess, Olaf and Gasser, Thomas and Van Broeckhoven, Christine and Theuns, Jessie and Aasly, Jan and Annesi, Grazia and Bentivoglio, Anna Rita and Brice, Alexis and Djarmati, Ana and Elbaz, Alexis and Farrer, Matthew and Ferrarese, Carlo and Gibson, J. Mark and Hadjigeorgiou, Georgios M. and Hattori, Nobutaka and Ioannidis, John P A and Jasinska-Myga, Barbara and Klein, Christine and Lambert, Jean-Charles and Lesage, Suzanne and Lin, Juei-Jueng and Lynch, Timothy and Mellick, George D. and de Nigris, Francesa and Opala, Grzegorz and Prigione, Alessandro and Quattrone, Aldo and Ross, Owen A. and Satake, Wataru and Silburn, Peter A. and Tan, Eng-King and Toda, Tatsushi and Tomiyama, Hiroyuki and Wirdefeldt, Karin and Wszolek, Zbigniew K and Xiromerisiou, Georgia and Maraganore, Demetrius M. and ,  and Puschmann, Andreas},
  issn         = {1558-1497},
  keyword      = {Aged,Chi-Square Distribution,Cohort Studies,European Continental Ancestry Group,Female,Gene Frequency,Genetic Predisposition to Disease,Genome-Wide Association Study,Genotype,Humans,International Cooperation,Male,Meta-Analysis as Topic,Middle Aged,Mitochondrial Proteins,Parkinson Disease,Polymorphism, Single Nucleotide,Serine Endopeptidases,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {9--548},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2009.11.021},
  volume       = {32},
  year         = {2011},
}