A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
Identifieur interne : 000B92 ( Ncbi/Checkpoint ); précédent : 000B91; suivant : 000B93A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
Auteurs : Rejko Krüger [Allemagne] ; 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 Klein ; Jean-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 Wszolek ; Georgia Xiromerisiou ; Demetrius M. MaraganoreSource :
- Neurobiology of aging [ 1558-1497 ] ; 2011.
English descriptors
- KwdEn :
- Aged, Chi-Square Distribution, Cohort Studies, European Continental Ancestry Group (ethnology), Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Meta-Analysis as Topic, Middle Aged, Mitochondrial Proteins (genetics), Parkinson Disease (epidemiology), Parkinson Disease (ethnology), Parkinson Disease (genetics), Polymorphism, Single Nucleotide (genetics), Serine Endopeptidases (genetics).
- MESH :
- chemical , genetics : Mitochondrial Proteins, Serine Endopeptidases.
- epidemiology : Parkinson Disease.
- ethnology : European Continental Ancestry Group, Parkinson Disease.
- genetics : Parkinson Disease, Polymorphism, Single Nucleotide.
- Aged, Chi-Square Distribution, Cohort Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Meta-Analysis as Topic, Middle Aged.
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; 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.
DOI: 10.1016/j.neurobiolaging.2009.11.021
PubMed: 20036034
Affiliations:
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Maraganore</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:20036034</idno><idno type="pmid">20036034</idno><idno type="doi">10.1016/j.neurobiolaging.2009.11.021</idno><idno type="wicri:Area/PubMed/Corpus">000C41</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C41</idno><idno type="wicri:Area/PubMed/Curation">000C41</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C41</idno><idno type="wicri:Area/PubMed/Checkpoint">000C41</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C41</idno><idno type="wicri:Area/Ncbi/Merge">000B92</idno><idno type="wicri:Area/Ncbi/Curation">000B92</idno><idno type="wicri:Area/Ncbi/Checkpoint">000B92</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.</title><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Functional Neurogenomics, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany. rejko.krueger@uni-tuebingen.de</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Functional Neurogenomics, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen</wicri:regionArea><wicri:noRegion>University of Tübingen</wicri:noRegion><wicri:noRegion>University of Tübingen</wicri:noRegion><wicri:noRegion>University of Tübingen</wicri:noRegion></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name></author><author><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name></author><author><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</name></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name></author><author><name sortKey="Bentivoglio, Anna Rita" sort="Bentivoglio, Anna Rita" uniqKey="Bentivoglio A" first="Anna Rita" last="Bentivoglio">Anna Rita Bentivoglio</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author><author><name sortKey="Djarmati, Ana" sort="Djarmati, Ana" uniqKey="Djarmati A" first="Ana" last="Djarmati">Ana Djarmati</name></author><author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name></author><author><name sortKey="Gibson, J Mark" sort="Gibson, J Mark" uniqKey="Gibson J" first="J Mark" last="Gibson">J Mark Gibson</name></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></author><author><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name></author><author><name sortKey="De Nigris, Francesa" sort="De Nigris, Francesa" uniqKey="De Nigris F" first="Francesa" last="De Nigris">Francesa De Nigris</name></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name></author><author><name sortKey="Prigione, Alessandro" sort="Prigione, Alessandro" uniqKey="Prigione A" first="Alessandro" last="Prigione">Alessandro Prigione</name></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A" last="Silburn">Peter A. Silburn</name></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng King" last="Tan">Eng King Tan</name></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name></author><author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></author><author><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name></author><author><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M" last="Maraganore">Demetrius M. Maraganore</name></author></analytic><series><title level="j">Neurobiology of aging</title><idno type="eISSN">1558-1497</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Chi-Square Distribution</term><term>Cohort Studies</term><term>European Continental Ancestry Group (ethnology)</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Genotype</term><term>Humans</term><term>International Cooperation</term><term>Male</term><term>Meta-Analysis as Topic</term><term>Middle Aged</term><term>Mitochondrial Proteins (genetics)</term><term>Parkinson Disease (epidemiology)</term><term>Parkinson Disease (ethnology)</term><term>Parkinson Disease (genetics)</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Serine Endopeptidases (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Mitochondrial Proteins</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="ethnology" xml:lang="en"><term>European Continental Ancestry Group</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Chi-Square Distribution</term><term>Cohort Studies</term><term>Female</term><term>Gene Frequency</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Genotype</term><term>Humans</term><term>International Cooperation</term><term>Male</term><term>Meta-Analysis as Topic</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><noCountry><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</name><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><name sortKey="Bentivoglio, Anna Rita" sort="Bentivoglio, Anna Rita" uniqKey="Bentivoglio A" first="Anna Rita" last="Bentivoglio">Anna Rita Bentivoglio</name><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><name sortKey="De Nigris, Francesa" sort="De Nigris, Francesa" uniqKey="De Nigris F" first="Francesa" last="De Nigris">Francesa De Nigris</name><name sortKey="Djarmati, Ana" sort="Djarmati, Ana" uniqKey="Djarmati A" first="Ana" last="Djarmati">Ana Djarmati</name><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><name sortKey="Gibson, J Mark" sort="Gibson, J Mark" uniqKey="Gibson J" first="J Mark" last="Gibson">J Mark Gibson</name><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M" last="Maraganore">Demetrius M. Maraganore</name><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><name sortKey="Prigione, Alessandro" sort="Prigione, Alessandro" uniqKey="Prigione A" first="Alessandro" last="Prigione">Alessandro Prigione</name><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A" last="Silburn">Peter A. Silburn</name><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng King" last="Tan">Eng King Tan</name><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|clé= pubmed:20036034
|texte= A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
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